Conference Coverage

BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. 

In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.

“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. 

There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.

 

Are Milder Cases the Ones Being Missed?

Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”

She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” 

She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” 

However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
 

Is Wisconsin Representative of Cushing Everywhere?

Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. 

The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. 

A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. 

However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. 

Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. 

On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted. 

Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. 

Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. 
 

A version of this article appeared on Medscape.com.

BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. 

In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.

“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. 

There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.

 

Are Milder Cases the Ones Being Missed?

Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”

She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” 

She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” 

However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
 

Is Wisconsin Representative of Cushing Everywhere?

Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. 

The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. 

A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. 

However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. 

Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. 

On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted. 

Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. 

Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. 
 

A version of this article appeared on Medscape.com.

BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. 

In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.

“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. 

There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.

 

Are Milder Cases the Ones Being Missed?

Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”

She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” 

She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” 

However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
 

Is Wisconsin Representative of Cushing Everywhere?

Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. 

The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. 

A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. 

However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. 

Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. 

On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted. 

Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. 

Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. 
 

A version of this article appeared on Medscape.com.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).

Otoe Sugahara manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group’s work at ENDO 2024, the Endocrine Society’s annual meeting in Boston. 

“Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations,” Ms. Sugahara said in a statement released by the Endocrine Society.

For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Ms. Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.

“While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients,” Ms. Sugahara and coauthors said in an abstract provided by the Endocrine Society.

Ms. Sugahara’s report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.

These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC’s VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.

Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Dr. Sempos, now retired, said in an interview. And, in his view, it’s something that busy practitioners should not have to consider.

“They have literally thousands of diseases they have to be able to recognize and diagnose,” Dr. Sempos said. “They should be able to count on the laboratory system to give them accurate and precise data.”
 

‘Nudging’ Toward Better Results

The CDC’s certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests. 

This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told this news organization. It helps by “nudging manufacturers in the right direction,” he said.

“Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing,” said Dr. Hoofnagle, who is also chair of the Accuracy-Based Programs Committee of the College of American Pathologists.

“There are still many immunoassays on the market that aren’t giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction,” he said.

US scientists use two main types of technologies to measure vitamin D in the blood, Ms. Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.

At the ENDO 2024 meeting, Ms. Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests’ bias, or the deviation of test results from the true value, as determined with the CDC’s reference method for vitamin D.

Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Ms. Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Ms. Sugahara reported. 

These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told this news organization in an email exchange.

The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
 

Call for Research

Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it. 

The Endocrine Society’s newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.

Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.

‘”Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population,” they wrote.

It’s uncertain that “any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective,” Dr. Demay and coauthors added.

They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests. 

The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That’s the same grade the task force gave it in 2014.

The USPSTF uses a grade of D to recommend against use of a test or service.

In an interview with this news organization, John Wong, MD, vice chair of the USPSTF, reiterated his group’s call for more research into the potential benefits and harms of vitamin D screening. 

One of the challenges in addressing this issue, Dr. Wong noted, has been the variability of test results. Therefore, efforts such as the CDC’s VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.

Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don’t have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.

“We really would like to have that evidence because we recognize that it’s an important health question to help everybody in this nation stay healthy and live longer,” Dr. Wong said.

A version of this article appeared on Medscape.com.

Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).

Otoe Sugahara manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group’s work at ENDO 2024, the Endocrine Society’s annual meeting in Boston. 

“Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations,” Ms. Sugahara said in a statement released by the Endocrine Society.

For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Ms. Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.

“While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients,” Ms. Sugahara and coauthors said in an abstract provided by the Endocrine Society.

Ms. Sugahara’s report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.

These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC’s VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.

Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Dr. Sempos, now retired, said in an interview. And, in his view, it’s something that busy practitioners should not have to consider.

“They have literally thousands of diseases they have to be able to recognize and diagnose,” Dr. Sempos said. “They should be able to count on the laboratory system to give them accurate and precise data.”
 

‘Nudging’ Toward Better Results

The CDC’s certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests. 

This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told this news organization. It helps by “nudging manufacturers in the right direction,” he said.

“Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing,” said Dr. Hoofnagle, who is also chair of the Accuracy-Based Programs Committee of the College of American Pathologists.

“There are still many immunoassays on the market that aren’t giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction,” he said.

US scientists use two main types of technologies to measure vitamin D in the blood, Ms. Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.

At the ENDO 2024 meeting, Ms. Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests’ bias, or the deviation of test results from the true value, as determined with the CDC’s reference method for vitamin D.

Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Ms. Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Ms. Sugahara reported. 

These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told this news organization in an email exchange.

The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
 

Call for Research

Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it. 

The Endocrine Society’s newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.

Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.

‘”Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population,” they wrote.

It’s uncertain that “any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective,” Dr. Demay and coauthors added.

They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests. 

The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That’s the same grade the task force gave it in 2014.

The USPSTF uses a grade of D to recommend against use of a test or service.

In an interview with this news organization, John Wong, MD, vice chair of the USPSTF, reiterated his group’s call for more research into the potential benefits and harms of vitamin D screening. 

One of the challenges in addressing this issue, Dr. Wong noted, has been the variability of test results. Therefore, efforts such as the CDC’s VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.

Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don’t have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.

“We really would like to have that evidence because we recognize that it’s an important health question to help everybody in this nation stay healthy and live longer,” Dr. Wong said.

A version of this article appeared on Medscape.com.

Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).

Otoe Sugahara manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group’s work at ENDO 2024, the Endocrine Society’s annual meeting in Boston. 

“Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations,” Ms. Sugahara said in a statement released by the Endocrine Society.

For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Ms. Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.

“While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients,” Ms. Sugahara and coauthors said in an abstract provided by the Endocrine Society.

Ms. Sugahara’s report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.

These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC’s VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.

Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Dr. Sempos, now retired, said in an interview. And, in his view, it’s something that busy practitioners should not have to consider.

“They have literally thousands of diseases they have to be able to recognize and diagnose,” Dr. Sempos said. “They should be able to count on the laboratory system to give them accurate and precise data.”
 

‘Nudging’ Toward Better Results

The CDC’s certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests. 

This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told this news organization. It helps by “nudging manufacturers in the right direction,” he said.

“Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing,” said Dr. Hoofnagle, who is also chair of the Accuracy-Based Programs Committee of the College of American Pathologists.

“There are still many immunoassays on the market that aren’t giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction,” he said.

US scientists use two main types of technologies to measure vitamin D in the blood, Ms. Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.

At the ENDO 2024 meeting, Ms. Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests’ bias, or the deviation of test results from the true value, as determined with the CDC’s reference method for vitamin D.

Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Ms. Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Ms. Sugahara reported. 

These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told this news organization in an email exchange.

The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
 

Call for Research

Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it. 

The Endocrine Society’s newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.

Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.

‘”Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population,” they wrote.

It’s uncertain that “any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective,” Dr. Demay and coauthors added.

They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests. 

The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That’s the same grade the task force gave it in 2014.

The USPSTF uses a grade of D to recommend against use of a test or service.

In an interview with this news organization, John Wong, MD, vice chair of the USPSTF, reiterated his group’s call for more research into the potential benefits and harms of vitamin D screening. 

One of the challenges in addressing this issue, Dr. Wong noted, has been the variability of test results. Therefore, efforts such as the CDC’s VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.

Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don’t have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.

“We really would like to have that evidence because we recognize that it’s an important health question to help everybody in this nation stay healthy and live longer,” Dr. Wong said.

A version of this article appeared on Medscape.com.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

Adults with hypersensitivity pneumonitis (HP) expressed interest in more knowledge of prognosis, etiology, treatment, and living well with the disease, based on new survey data presented at the American Thoracic Society International Conference.

HP is caused by environmental exposure and is often incurable, and patients are challenged with identifying and mitigating the exposure with limited guidance, wrote Janani Varadarajan, MD, of Weill Cornell Medicine, New York, and colleagues. 

“Lack of knowledge about HP and its therapeutics contributes to significant uncertainty and impacts quality of life,” the researchers wrote in their abstract. 

Surveys Conducted to Understand Patient Concerns

To better identify patient-perceived HP knowledge gaps and develop educational resources, the researchers assessed 21 adults diagnosed with HP. Patients underwent interviews using nominal group technique (NGT) for group consensus and completed a survey on educational preferences. The mean age of the participants was 69.5 years, and 81% were women.

The researchers conducted five NGTs. Participants were asked two questions: What questions about your HP do you have that keep you awake at night?” and “What information do you want about your HP that you cannot find?” They also voted on responses that were grouped by theme.

The top themes that emerged from the interviews were concerns about natural history and prognosis of HP (28.3%), current treatment options and therapeutic research (22.5%), epidemiology and etiology (17.5%), living well with HP (15.4%), origin and management of symptoms (8.3%), identifying and mitigating exposures (4.6%), and methods of information uptake and dissemination (3.3%).

The findings were limited by the relatively small sample size. However, the results will inform the development of educational materials on the virtual Patient Activated Learning System, the researchers noted in their abstract. “This curriculum will be a component of a larger support intervention that aims to improve patient knowledge, self-efficacy, and HRQOL [health-related quality of life],” they said.

Findings Will Fuel Needed Education

Recognizing more interstitial lung disease (ILD) has led to diagnosing more hypersensitivity pneumonitis, and it is important to keep patients’ concerns in mind, said Aamir Ajmeri, MD, assistant professor of clinical thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“If patients research ILD online, most of the literature is based on idiopathic pulmonary fibrosis,” he said. “IPF literature can be frightening because patients will see a median 2- to 5-year survival rate from time of diagnosis, the need for lung transplant, and progressive hypoxemia; however, all of this may not be true in HP,” he noted. 

“HP is more of a spectrum, but it is more difficult for patient to understand when we say ‘your lungs have reacted to something in your environment,’ and they will ask ‘what can I do to change this?’” Dr. Ajmeri told this news organization. “That is why these types of studies, where we recognize what patients need and how they can learn more about their diagnosis, are very important,” he said.

The study findings were not surprising, Dr. Ajmeri said. “We have a large cohort of patients with HP at Temple Health, and these are the same questions they ask me and my colleagues,” he said. “It can be tough for patients to grasp this diagnosis. We know it is related to something inhaled from the environment, but it may be difficult to pinpoint,” he said.

In patient-centered research, patients can help shed light onto the needs that are unmet for the disease process by asking hypothesis-generating questions, Dr. Ajmeri said. For example, he said he is frequently asked by patients why HP continues to recur after they have remediated a home (potential source of exposure) and been on medication.

“The study was limited in part by the small sample size but captured a good representation of what patients are asking their physicians about,” Dr. Ajmeri said. Although it is always preferable to have more patients, the findings are important, “and the educational materials that they will lead to are greatly needed,” he said.

The study was supported by the Stony Wold-Herbert Fund, the American Lung Association Catalyst Award, and the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Ajmeri had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Adults with hypersensitivity pneumonitis (HP) expressed interest in more knowledge of prognosis, etiology, treatment, and living well with the disease, based on new survey data presented at the American Thoracic Society International Conference.

HP is caused by environmental exposure and is often incurable, and patients are challenged with identifying and mitigating the exposure with limited guidance, wrote Janani Varadarajan, MD, of Weill Cornell Medicine, New York, and colleagues. 

“Lack of knowledge about HP and its therapeutics contributes to significant uncertainty and impacts quality of life,” the researchers wrote in their abstract. 

Surveys Conducted to Understand Patient Concerns

To better identify patient-perceived HP knowledge gaps and develop educational resources, the researchers assessed 21 adults diagnosed with HP. Patients underwent interviews using nominal group technique (NGT) for group consensus and completed a survey on educational preferences. The mean age of the participants was 69.5 years, and 81% were women.

The researchers conducted five NGTs. Participants were asked two questions: What questions about your HP do you have that keep you awake at night?” and “What information do you want about your HP that you cannot find?” They also voted on responses that were grouped by theme.

The top themes that emerged from the interviews were concerns about natural history and prognosis of HP (28.3%), current treatment options and therapeutic research (22.5%), epidemiology and etiology (17.5%), living well with HP (15.4%), origin and management of symptoms (8.3%), identifying and mitigating exposures (4.6%), and methods of information uptake and dissemination (3.3%).

The findings were limited by the relatively small sample size. However, the results will inform the development of educational materials on the virtual Patient Activated Learning System, the researchers noted in their abstract. “This curriculum will be a component of a larger support intervention that aims to improve patient knowledge, self-efficacy, and HRQOL [health-related quality of life],” they said.

Findings Will Fuel Needed Education

Recognizing more interstitial lung disease (ILD) has led to diagnosing more hypersensitivity pneumonitis, and it is important to keep patients’ concerns in mind, said Aamir Ajmeri, MD, assistant professor of clinical thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“If patients research ILD online, most of the literature is based on idiopathic pulmonary fibrosis,” he said. “IPF literature can be frightening because patients will see a median 2- to 5-year survival rate from time of diagnosis, the need for lung transplant, and progressive hypoxemia; however, all of this may not be true in HP,” he noted. 

“HP is more of a spectrum, but it is more difficult for patient to understand when we say ‘your lungs have reacted to something in your environment,’ and they will ask ‘what can I do to change this?’” Dr. Ajmeri told this news organization. “That is why these types of studies, where we recognize what patients need and how they can learn more about their diagnosis, are very important,” he said.

The study findings were not surprising, Dr. Ajmeri said. “We have a large cohort of patients with HP at Temple Health, and these are the same questions they ask me and my colleagues,” he said. “It can be tough for patients to grasp this diagnosis. We know it is related to something inhaled from the environment, but it may be difficult to pinpoint,” he said.

In patient-centered research, patients can help shed light onto the needs that are unmet for the disease process by asking hypothesis-generating questions, Dr. Ajmeri said. For example, he said he is frequently asked by patients why HP continues to recur after they have remediated a home (potential source of exposure) and been on medication.

“The study was limited in part by the small sample size but captured a good representation of what patients are asking their physicians about,” Dr. Ajmeri said. Although it is always preferable to have more patients, the findings are important, “and the educational materials that they will lead to are greatly needed,” he said.

The study was supported by the Stony Wold-Herbert Fund, the American Lung Association Catalyst Award, and the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Ajmeri had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Adults with hypersensitivity pneumonitis (HP) expressed interest in more knowledge of prognosis, etiology, treatment, and living well with the disease, based on new survey data presented at the American Thoracic Society International Conference.

HP is caused by environmental exposure and is often incurable, and patients are challenged with identifying and mitigating the exposure with limited guidance, wrote Janani Varadarajan, MD, of Weill Cornell Medicine, New York, and colleagues. 

“Lack of knowledge about HP and its therapeutics contributes to significant uncertainty and impacts quality of life,” the researchers wrote in their abstract. 

Surveys Conducted to Understand Patient Concerns

To better identify patient-perceived HP knowledge gaps and develop educational resources, the researchers assessed 21 adults diagnosed with HP. Patients underwent interviews using nominal group technique (NGT) for group consensus and completed a survey on educational preferences. The mean age of the participants was 69.5 years, and 81% were women.

The researchers conducted five NGTs. Participants were asked two questions: What questions about your HP do you have that keep you awake at night?” and “What information do you want about your HP that you cannot find?” They also voted on responses that were grouped by theme.

The top themes that emerged from the interviews were concerns about natural history and prognosis of HP (28.3%), current treatment options and therapeutic research (22.5%), epidemiology and etiology (17.5%), living well with HP (15.4%), origin and management of symptoms (8.3%), identifying and mitigating exposures (4.6%), and methods of information uptake and dissemination (3.3%).

The findings were limited by the relatively small sample size. However, the results will inform the development of educational materials on the virtual Patient Activated Learning System, the researchers noted in their abstract. “This curriculum will be a component of a larger support intervention that aims to improve patient knowledge, self-efficacy, and HRQOL [health-related quality of life],” they said.

Findings Will Fuel Needed Education

Recognizing more interstitial lung disease (ILD) has led to diagnosing more hypersensitivity pneumonitis, and it is important to keep patients’ concerns in mind, said Aamir Ajmeri, MD, assistant professor of clinical thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“If patients research ILD online, most of the literature is based on idiopathic pulmonary fibrosis,” he said. “IPF literature can be frightening because patients will see a median 2- to 5-year survival rate from time of diagnosis, the need for lung transplant, and progressive hypoxemia; however, all of this may not be true in HP,” he noted. 

“HP is more of a spectrum, but it is more difficult for patient to understand when we say ‘your lungs have reacted to something in your environment,’ and they will ask ‘what can I do to change this?’” Dr. Ajmeri told this news organization. “That is why these types of studies, where we recognize what patients need and how they can learn more about their diagnosis, are very important,” he said.

The study findings were not surprising, Dr. Ajmeri said. “We have a large cohort of patients with HP at Temple Health, and these are the same questions they ask me and my colleagues,” he said. “It can be tough for patients to grasp this diagnosis. We know it is related to something inhaled from the environment, but it may be difficult to pinpoint,” he said.

In patient-centered research, patients can help shed light onto the needs that are unmet for the disease process by asking hypothesis-generating questions, Dr. Ajmeri said. For example, he said he is frequently asked by patients why HP continues to recur after they have remediated a home (potential source of exposure) and been on medication.

“The study was limited in part by the small sample size but captured a good representation of what patients are asking their physicians about,” Dr. Ajmeri said. Although it is always preferable to have more patients, the findings are important, “and the educational materials that they will lead to are greatly needed,” he said.

The study was supported by the Stony Wold-Herbert Fund, the American Lung Association Catalyst Award, and the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Ajmeri had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

In the common challenge of patients with relapsed multiple myeloma who are refractory to lenalidomide after receiving frontline treatment with the drug, treatment with the first-in-class, antibody-drug conjugate belantamab mafodotin, along with pomalidomide plus dexamethasone (pom-dex), shows significant improvement in durability and progression-free survival (PFS) over the standard of care approach.

“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.

The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).

The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).

The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.

The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.

While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.

Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.

In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.

Discontinuation rates for fatal or AEs of any cause were similar in both arms.

The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).

The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.

As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.

The AEs resulted in treatment discontinuation for 9% of patients.

The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.

“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.

Previous FDA Approval Withdrawn

Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).

However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.

Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”

While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”

Antibody-Drug Conjugates: Less is More?

The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”

In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).

In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”

He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”

“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.

“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.

That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”

And “less ocular toxicity with similar efficacy are big wins,” he added.

“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”

Other Therapies

In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.

Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.

While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.

“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.

The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.

The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.

In the common challenge of patients with relapsed multiple myeloma who are refractory to lenalidomide after receiving frontline treatment with the drug, treatment with the first-in-class, antibody-drug conjugate belantamab mafodotin, along with pomalidomide plus dexamethasone (pom-dex), shows significant improvement in durability and progression-free survival (PFS) over the standard of care approach.

“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.

The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).

The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).

The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.

The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.

While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.

Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.

In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.

Discontinuation rates for fatal or AEs of any cause were similar in both arms.

The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).

The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.

As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.

The AEs resulted in treatment discontinuation for 9% of patients.

The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.

“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.

Previous FDA Approval Withdrawn

Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).

However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.

Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”

While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”

Antibody-Drug Conjugates: Less is More?

The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”

In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).

In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”

He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”

“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.

“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.

That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”

And “less ocular toxicity with similar efficacy are big wins,” he added.

“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”

Other Therapies

In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.

Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.

While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.

“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.

The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.

The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.

In the common challenge of patients with relapsed multiple myeloma who are refractory to lenalidomide after receiving frontline treatment with the drug, treatment with the first-in-class, antibody-drug conjugate belantamab mafodotin, along with pomalidomide plus dexamethasone (pom-dex), shows significant improvement in durability and progression-free survival (PFS) over the standard of care approach.

“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.

The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).

The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).

The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.

The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.

While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.

Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.

In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.

Discontinuation rates for fatal or AEs of any cause were similar in both arms.

The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).

The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.

As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.

The AEs resulted in treatment discontinuation for 9% of patients.

The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.

“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.

Previous FDA Approval Withdrawn

Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).

However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.

Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”

While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”

Antibody-Drug Conjugates: Less is More?

The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”

In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).

In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”

He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”

“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.

“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.

That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”

And “less ocular toxicity with similar efficacy are big wins,” he added.

“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”

Other Therapies

In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.

Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.

While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.

“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.

The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.

The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.