Conference Coverage

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Among people diagnosed with cutaneous melanoma in the United States, those who live in rural areas have significantly lower rates of survival than those who live in urban areas, results from an analysis of data from the National Cancer Institute showed.

“Melanoma is currently the fifth most common malignancy in the United States, with approximately 106,000 new cases and 7180 reported deaths occurring in 2021,” the study’s first author, Mitchell Taylor, MD, a dermatology research fellow at the University of Nebraska, Omaha, and colleagues wrote in the abstract, which was presented during a poster session at the annual meeting of the Society for Investigative Dermatology. “Rural areas have been shown to bear a higher melanoma disease burden, yet there is a paucity of national-level studies examining these disparities.”

To characterize the rural population diagnosed with cutaneous melanoma and assess associated disparities in the United States, the researchers queried the NCI’s Surveillance, Epidemiology, and End Results database to identify individuals diagnosed with cutaneous melanoma from 2000 to 2020 (International Classification of Diseases, 3rd Edition, 8720/3 — 8780/3; Primary Site codes C44.0-C44.9). They drew from US Office of Management and Budget terminology to define and categorize rural and urban communities.

Among 391,047 patients included during the study period, binary logistic regression analysis revealed that patients in rural areas had a greater odds of being older, from ages 50 to 75 years (odds ratio [OR], 1.10; P < .001); had annual incomes < $70,000 (OR, 16.80; P < .001); had tumors located on the head and neck (OR, 1.24; P < .001); and presented with regional/distant disease (OR, 1.13; P < .001).

As for disease-specific survival, patients living in rural areas had significantly reduced survival compared with those living in urban areas (a mean of 207.3 vs 216.3 months, respectively; P < .001). Multivariate Cox regression revealed that living in a rural setting was significantly associated with reduced disease-specific survival (hazard ratio [HR], 1.10; P < .001), as was having head and neck tumors (HR, 1.41; P < .001).“Overall, this study underscores a significant decrease in disease-specific survival among rural patients diagnosed with cutaneous melanoma and establishes a significant association between rural living and high-risk primary tumor locations, particularly the head and neck,” the authors concluded.

Lucinda Kohn, MD, assistant professor of dermatology in the Centers for American Indian and Alaska Native Health at the University of Colorado at Denver, Aurora, Colorado, who was asked to comment on the results, said the findings echo the results of a recent study which characterized melanoma rates among non-Hispanic American Indian/Alaska Native individuals from 1999 to 2019.

“I suspect this decreased disease-specific survival highlights the issues our rural-residing patients face with access to dermatology care,” Dr. Kohn told this news organization. “Dermatologists are able to detect thinner melanomas than patients [and] are preferentially concentrated in metropolitan areas. Dermatologists are also the most skilled and knowledgeable to screen, diagnose, and manage melanomas. Having fewer dermatologists in rural areas impedes melanoma care for our rural-residing patients.”

Neither the researchers nor Dr. Kohn reported any relevant disclosures.

A version of this article first appeared on Medscape.com.

Among people diagnosed with cutaneous melanoma in the United States, those who live in rural areas have significantly lower rates of survival than those who live in urban areas, results from an analysis of data from the National Cancer Institute showed.

“Melanoma is currently the fifth most common malignancy in the United States, with approximately 106,000 new cases and 7180 reported deaths occurring in 2021,” the study’s first author, Mitchell Taylor, MD, a dermatology research fellow at the University of Nebraska, Omaha, and colleagues wrote in the abstract, which was presented during a poster session at the annual meeting of the Society for Investigative Dermatology. “Rural areas have been shown to bear a higher melanoma disease burden, yet there is a paucity of national-level studies examining these disparities.”

To characterize the rural population diagnosed with cutaneous melanoma and assess associated disparities in the United States, the researchers queried the NCI’s Surveillance, Epidemiology, and End Results database to identify individuals diagnosed with cutaneous melanoma from 2000 to 2020 (International Classification of Diseases, 3rd Edition, 8720/3 — 8780/3; Primary Site codes C44.0-C44.9). They drew from US Office of Management and Budget terminology to define and categorize rural and urban communities.

Among 391,047 patients included during the study period, binary logistic regression analysis revealed that patients in rural areas had a greater odds of being older, from ages 50 to 75 years (odds ratio [OR], 1.10; P < .001); had annual incomes < $70,000 (OR, 16.80; P < .001); had tumors located on the head and neck (OR, 1.24; P < .001); and presented with regional/distant disease (OR, 1.13; P < .001).

As for disease-specific survival, patients living in rural areas had significantly reduced survival compared with those living in urban areas (a mean of 207.3 vs 216.3 months, respectively; P < .001). Multivariate Cox regression revealed that living in a rural setting was significantly associated with reduced disease-specific survival (hazard ratio [HR], 1.10; P < .001), as was having head and neck tumors (HR, 1.41; P < .001).“Overall, this study underscores a significant decrease in disease-specific survival among rural patients diagnosed with cutaneous melanoma and establishes a significant association between rural living and high-risk primary tumor locations, particularly the head and neck,” the authors concluded.

Lucinda Kohn, MD, assistant professor of dermatology in the Centers for American Indian and Alaska Native Health at the University of Colorado at Denver, Aurora, Colorado, who was asked to comment on the results, said the findings echo the results of a recent study which characterized melanoma rates among non-Hispanic American Indian/Alaska Native individuals from 1999 to 2019.

“I suspect this decreased disease-specific survival highlights the issues our rural-residing patients face with access to dermatology care,” Dr. Kohn told this news organization. “Dermatologists are able to detect thinner melanomas than patients [and] are preferentially concentrated in metropolitan areas. Dermatologists are also the most skilled and knowledgeable to screen, diagnose, and manage melanomas. Having fewer dermatologists in rural areas impedes melanoma care for our rural-residing patients.”

Neither the researchers nor Dr. Kohn reported any relevant disclosures.

A version of this article first appeared on Medscape.com.

Among people diagnosed with cutaneous melanoma in the United States, those who live in rural areas have significantly lower rates of survival than those who live in urban areas, results from an analysis of data from the National Cancer Institute showed.

“Melanoma is currently the fifth most common malignancy in the United States, with approximately 106,000 new cases and 7180 reported deaths occurring in 2021,” the study’s first author, Mitchell Taylor, MD, a dermatology research fellow at the University of Nebraska, Omaha, and colleagues wrote in the abstract, which was presented during a poster session at the annual meeting of the Society for Investigative Dermatology. “Rural areas have been shown to bear a higher melanoma disease burden, yet there is a paucity of national-level studies examining these disparities.”

To characterize the rural population diagnosed with cutaneous melanoma and assess associated disparities in the United States, the researchers queried the NCI’s Surveillance, Epidemiology, and End Results database to identify individuals diagnosed with cutaneous melanoma from 2000 to 2020 (International Classification of Diseases, 3rd Edition, 8720/3 — 8780/3; Primary Site codes C44.0-C44.9). They drew from US Office of Management and Budget terminology to define and categorize rural and urban communities.

Among 391,047 patients included during the study period, binary logistic regression analysis revealed that patients in rural areas had a greater odds of being older, from ages 50 to 75 years (odds ratio [OR], 1.10; P < .001); had annual incomes < $70,000 (OR, 16.80; P < .001); had tumors located on the head and neck (OR, 1.24; P < .001); and presented with regional/distant disease (OR, 1.13; P < .001).

As for disease-specific survival, patients living in rural areas had significantly reduced survival compared with those living in urban areas (a mean of 207.3 vs 216.3 months, respectively; P < .001). Multivariate Cox regression revealed that living in a rural setting was significantly associated with reduced disease-specific survival (hazard ratio [HR], 1.10; P < .001), as was having head and neck tumors (HR, 1.41; P < .001).“Overall, this study underscores a significant decrease in disease-specific survival among rural patients diagnosed with cutaneous melanoma and establishes a significant association between rural living and high-risk primary tumor locations, particularly the head and neck,” the authors concluded.

Lucinda Kohn, MD, assistant professor of dermatology in the Centers for American Indian and Alaska Native Health at the University of Colorado at Denver, Aurora, Colorado, who was asked to comment on the results, said the findings echo the results of a recent study which characterized melanoma rates among non-Hispanic American Indian/Alaska Native individuals from 1999 to 2019.

“I suspect this decreased disease-specific survival highlights the issues our rural-residing patients face with access to dermatology care,” Dr. Kohn told this news organization. “Dermatologists are able to detect thinner melanomas than patients [and] are preferentially concentrated in metropolitan areas. Dermatologists are also the most skilled and knowledgeable to screen, diagnose, and manage melanomas. Having fewer dermatologists in rural areas impedes melanoma care for our rural-residing patients.”

Neither the researchers nor Dr. Kohn reported any relevant disclosures.

A version of this article first appeared on Medscape.com.

Compared with White patients with Merkel cell carcinoma (MCC), non-White Hispanic patients more commonly presented younger than 70 years of age and were more often female. In addition, the most affected site was the upper limb/shoulder, which differs from what has been reported in previous studies.

Those are key findings from a retrospective study of national cancer data that was presented during a poster session at the annual meeting of the Society for Investigative Dermatology.

“Merkel cell carcinoma is an infrequent and aggressive form of neuroendocrine skin cancer that mainly impacts individuals of White ethnicity, with a general occurrence rate of 0.7 instances per 100,000 person-years,” one of the study authors, Luis J. Borda, MD, chief dermatology resident at Eastern Virginia Medical School, Norfolk, Virginia, told this news organization. The incidence of MCC is increasing among all racial groups, especially in the Hispanic population, he added.

To determine how age, sex, and primary site of MCC differ in White vs non-White Hispanic patients, the researchers evaluated the 22 population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program from 2000 through 2020. They reported categorical variables as counts and percentages and used chi-square test with Yates’s correction to assess the association between categorical variables.

Of the 17,920 MCCs identified by the researchers, 40 (0.22%) were in non-White Hispanic patients. Compared with the White patients with MCC, significantly fewer non-White Hispanic patients were age 70 years or older (50% vs 72.1%, respectively; P < .001), and MCC was more common in female non-White Hispanic patients (23, or 57.5%), while White patients with MCC were predominantly male (11,309, or 63.2%; P < .05). “This suggests that MCC in non-White Hispanic patients may involve different risk factors related to age beyond just cumulative UV exposure and aging-related immunosenescence, which may additionally account for the higher prevalence of females in this cohort, as historically male outdoor occupation has resulted in increased lifetime cumulative UV exposure,” Dr. Borda said.

The head and neck were the most common sites of disease involvement in White patients (41.9% vs 27.5% in non-White Hispanic patients; P = .09), while the upper limb and shoulder were the most common sites of disease involvement in non-White Hispanic patients (37.5% vs 23.8% in White patients; P = .06). This finding “differs from previous studies showing head/neck being the most common site in Hispanics,” Dr. Borda said, adding that this could be a result of White patients not being included in the Hispanic cohort in this study. “Because non-White Hispanic patients have darker skin, they may have proportionally more cases on sun-protected skin, as is described by the present data, suggesting that they are less likely to have UV-driven MCC.”

The study “highlights distinct demographic and clinical characteristics of MCC among non-White Hispanic patients compared to their White counterparts, emphasizing the importance of considering race/ethnicity in understanding the epidemiology of this rare but increasingly prevalent cancer,” Dr. Borda said. He and his co-authors are planning to do further research on the increasing incidence of MCC in non-White Hispanic patients and on staging at diagnosis compared to White patients.

Dr. Borda acknowledged certain limitations of the analysis, including the small sample size in the non-White Hispanic group, the retrospective nature of SEER data, selection bias, and the potential for underreporting. He and his co-authors reported having no financial disclosures.

A version of this article first appeared on Medscape.com.

Compared with White patients with Merkel cell carcinoma (MCC), non-White Hispanic patients more commonly presented younger than 70 years of age and were more often female. In addition, the most affected site was the upper limb/shoulder, which differs from what has been reported in previous studies.

Those are key findings from a retrospective study of national cancer data that was presented during a poster session at the annual meeting of the Society for Investigative Dermatology.

“Merkel cell carcinoma is an infrequent and aggressive form of neuroendocrine skin cancer that mainly impacts individuals of White ethnicity, with a general occurrence rate of 0.7 instances per 100,000 person-years,” one of the study authors, Luis J. Borda, MD, chief dermatology resident at Eastern Virginia Medical School, Norfolk, Virginia, told this news organization. The incidence of MCC is increasing among all racial groups, especially in the Hispanic population, he added.

To determine how age, sex, and primary site of MCC differ in White vs non-White Hispanic patients, the researchers evaluated the 22 population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program from 2000 through 2020. They reported categorical variables as counts and percentages and used chi-square test with Yates’s correction to assess the association between categorical variables.

Of the 17,920 MCCs identified by the researchers, 40 (0.22%) were in non-White Hispanic patients. Compared with the White patients with MCC, significantly fewer non-White Hispanic patients were age 70 years or older (50% vs 72.1%, respectively; P < .001), and MCC was more common in female non-White Hispanic patients (23, or 57.5%), while White patients with MCC were predominantly male (11,309, or 63.2%; P < .05). “This suggests that MCC in non-White Hispanic patients may involve different risk factors related to age beyond just cumulative UV exposure and aging-related immunosenescence, which may additionally account for the higher prevalence of females in this cohort, as historically male outdoor occupation has resulted in increased lifetime cumulative UV exposure,” Dr. Borda said.

The head and neck were the most common sites of disease involvement in White patients (41.9% vs 27.5% in non-White Hispanic patients; P = .09), while the upper limb and shoulder were the most common sites of disease involvement in non-White Hispanic patients (37.5% vs 23.8% in White patients; P = .06). This finding “differs from previous studies showing head/neck being the most common site in Hispanics,” Dr. Borda said, adding that this could be a result of White patients not being included in the Hispanic cohort in this study. “Because non-White Hispanic patients have darker skin, they may have proportionally more cases on sun-protected skin, as is described by the present data, suggesting that they are less likely to have UV-driven MCC.”

The study “highlights distinct demographic and clinical characteristics of MCC among non-White Hispanic patients compared to their White counterparts, emphasizing the importance of considering race/ethnicity in understanding the epidemiology of this rare but increasingly prevalent cancer,” Dr. Borda said. He and his co-authors are planning to do further research on the increasing incidence of MCC in non-White Hispanic patients and on staging at diagnosis compared to White patients.

Dr. Borda acknowledged certain limitations of the analysis, including the small sample size in the non-White Hispanic group, the retrospective nature of SEER data, selection bias, and the potential for underreporting. He and his co-authors reported having no financial disclosures.

A version of this article first appeared on Medscape.com.

Compared with White patients with Merkel cell carcinoma (MCC), non-White Hispanic patients more commonly presented younger than 70 years of age and were more often female. In addition, the most affected site was the upper limb/shoulder, which differs from what has been reported in previous studies.

Those are key findings from a retrospective study of national cancer data that was presented during a poster session at the annual meeting of the Society for Investigative Dermatology.

“Merkel cell carcinoma is an infrequent and aggressive form of neuroendocrine skin cancer that mainly impacts individuals of White ethnicity, with a general occurrence rate of 0.7 instances per 100,000 person-years,” one of the study authors, Luis J. Borda, MD, chief dermatology resident at Eastern Virginia Medical School, Norfolk, Virginia, told this news organization. The incidence of MCC is increasing among all racial groups, especially in the Hispanic population, he added.

To determine how age, sex, and primary site of MCC differ in White vs non-White Hispanic patients, the researchers evaluated the 22 population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program from 2000 through 2020. They reported categorical variables as counts and percentages and used chi-square test with Yates’s correction to assess the association between categorical variables.

Of the 17,920 MCCs identified by the researchers, 40 (0.22%) were in non-White Hispanic patients. Compared with the White patients with MCC, significantly fewer non-White Hispanic patients were age 70 years or older (50% vs 72.1%, respectively; P < .001), and MCC was more common in female non-White Hispanic patients (23, or 57.5%), while White patients with MCC were predominantly male (11,309, or 63.2%; P < .05). “This suggests that MCC in non-White Hispanic patients may involve different risk factors related to age beyond just cumulative UV exposure and aging-related immunosenescence, which may additionally account for the higher prevalence of females in this cohort, as historically male outdoor occupation has resulted in increased lifetime cumulative UV exposure,” Dr. Borda said.

The head and neck were the most common sites of disease involvement in White patients (41.9% vs 27.5% in non-White Hispanic patients; P = .09), while the upper limb and shoulder were the most common sites of disease involvement in non-White Hispanic patients (37.5% vs 23.8% in White patients; P = .06). This finding “differs from previous studies showing head/neck being the most common site in Hispanics,” Dr. Borda said, adding that this could be a result of White patients not being included in the Hispanic cohort in this study. “Because non-White Hispanic patients have darker skin, they may have proportionally more cases on sun-protected skin, as is described by the present data, suggesting that they are less likely to have UV-driven MCC.”

The study “highlights distinct demographic and clinical characteristics of MCC among non-White Hispanic patients compared to their White counterparts, emphasizing the importance of considering race/ethnicity in understanding the epidemiology of this rare but increasingly prevalent cancer,” Dr. Borda said. He and his co-authors are planning to do further research on the increasing incidence of MCC in non-White Hispanic patients and on staging at diagnosis compared to White patients.

Dr. Borda acknowledged certain limitations of the analysis, including the small sample size in the non-White Hispanic group, the retrospective nature of SEER data, selection bias, and the potential for underreporting. He and his co-authors reported having no financial disclosures.

A version of this article first appeared on Medscape.com.

MILAN — Fecal microbiota transplantation (FMT), also known as intestinal microbiota transplantation, significantly reduced recurrence of hepatic encephalopathy, compared with placebo, in patients with cirrhosis on standard-of-care treatment, results of a phase 2 randomized controlled trial show. 

“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.

Resetting the Gut

The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior. 

Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded. 

Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4). 

The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart. 

Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care. 

“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”

Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
 

One Dose of FMT Better Than None

Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%). 

SIP total/physical and psych scores improved with FMT (P = .003).

When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence. 

Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups. 

“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.

Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT. 

“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”

He pointed out that in smaller prior studies, the effects lasted up to 1 year. 
 

Setting the Stage for Phase 3 Trials

Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy. 

“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.

A version of this article appeared on Medscape.com.

MILAN — Fecal microbiota transplantation (FMT), also known as intestinal microbiota transplantation, significantly reduced recurrence of hepatic encephalopathy, compared with placebo, in patients with cirrhosis on standard-of-care treatment, results of a phase 2 randomized controlled trial show. 

“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.

Resetting the Gut

The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior. 

Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded. 

Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4). 

The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart. 

Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care. 

“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”

Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
 

One Dose of FMT Better Than None

Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%). 

SIP total/physical and psych scores improved with FMT (P = .003).

When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence. 

Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups. 

“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.

Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT. 

“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”

He pointed out that in smaller prior studies, the effects lasted up to 1 year. 
 

Setting the Stage for Phase 3 Trials

Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy. 

“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.

A version of this article appeared on Medscape.com.

MILAN — Fecal microbiota transplantation (FMT), also known as intestinal microbiota transplantation, significantly reduced recurrence of hepatic encephalopathy, compared with placebo, in patients with cirrhosis on standard-of-care treatment, results of a phase 2 randomized controlled trial show. 

“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.

Resetting the Gut

The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior. 

Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded. 

Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4). 

The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart. 

Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care. 

“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”

Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
 

One Dose of FMT Better Than None

Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%). 

SIP total/physical and psych scores improved with FMT (P = .003).

When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence. 

Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups. 

“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.

Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT. 

“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”

He pointed out that in smaller prior studies, the effects lasted up to 1 year. 
 

Setting the Stage for Phase 3 Trials

Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy. 

“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — Exercise has a long history in multiple sclerosis (MS). In 1838, the Scottish physician John Abercrombie reported that a patient with “a diminution of muscular power,” who could walk but only unsteadily, decided after various failed treatments like “evacuations and spare diet” to try “violent exercise.” He walked 5-6 miles on a warm evening, as quickly as he was able, and returned home “much fatigued, and considerably heated. Next morning he had severe pains in the calves of his legs, but his other complaints were much diminished, and in a few days disappeared. He has ever since enjoyed good health,” Dr. Abercrombie was quoted in Multiple Sclerosis: The History of a Disease by T. Jock Murray.

The first randomized, controlled trial of an exercise intervention for MS didn’t appear in the literature until 1988, but more than 200 have been published in the years since, according to Robert Motl, PhD, who spoke about exercise interventions for MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.

NASHVILLE, TENNESSEE — Exercise has a long history in multiple sclerosis (MS). In 1838, the Scottish physician John Abercrombie reported that a patient with “a diminution of muscular power,” who could walk but only unsteadily, decided after various failed treatments like “evacuations and spare diet” to try “violent exercise.” He walked 5-6 miles on a warm evening, as quickly as he was able, and returned home “much fatigued, and considerably heated. Next morning he had severe pains in the calves of his legs, but his other complaints were much diminished, and in a few days disappeared. He has ever since enjoyed good health,” Dr. Abercrombie was quoted in Multiple Sclerosis: The History of a Disease by T. Jock Murray.

The first randomized, controlled trial of an exercise intervention for MS didn’t appear in the literature until 1988, but more than 200 have been published in the years since, according to Robert Motl, PhD, who spoke about exercise interventions for MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.

NASHVILLE, TENNESSEE — Exercise has a long history in multiple sclerosis (MS). In 1838, the Scottish physician John Abercrombie reported that a patient with “a diminution of muscular power,” who could walk but only unsteadily, decided after various failed treatments like “evacuations and spare diet” to try “violent exercise.” He walked 5-6 miles on a warm evening, as quickly as he was able, and returned home “much fatigued, and considerably heated. Next morning he had severe pains in the calves of his legs, but his other complaints were much diminished, and in a few days disappeared. He has ever since enjoyed good health,” Dr. Abercrombie was quoted in Multiple Sclerosis: The History of a Disease by T. Jock Murray.

The first randomized, controlled trial of an exercise intervention for MS didn’t appear in the literature until 1988, but more than 200 have been published in the years since, according to Robert Motl, PhD, who spoke about exercise interventions for MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The addition of an anti-CD38 monoclonal antibody to the standard first-line combination treatment significantly improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), according to an interim analysis of an open-label, randomized, phase 3 trial.

Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published in The New England Journal of Medicine.

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.

According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy. 

“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”

For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.

The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.

The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).

At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.

An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).

The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).

As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.

“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.

In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.

“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”

Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”

In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”

However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”

As for adverse events, he said “they are what would be expected for a trial like this.”

Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.

Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”

In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.

All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”

The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.

The addition of an anti-CD38 monoclonal antibody to the standard first-line combination treatment significantly improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), according to an interim analysis of an open-label, randomized, phase 3 trial.

Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published in The New England Journal of Medicine.

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.

According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy. 

“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”

For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.

The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.

The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).

At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.

An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).

The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).

As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.

“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.

In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.

“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”

Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”

In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”

However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”

As for adverse events, he said “they are what would be expected for a trial like this.”

Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.

Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”

In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.

All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”

The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.

The addition of an anti-CD38 monoclonal antibody to the standard first-line combination treatment significantly improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), according to an interim analysis of an open-label, randomized, phase 3 trial.

Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published in The New England Journal of Medicine.

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.

According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy. 

“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”

For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.

The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.

The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).

At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.

An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).

The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).

As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.

“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.

In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.

“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”

Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”

In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”

However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”

As for adverse events, he said “they are what would be expected for a trial like this.”

Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.

Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”

In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.

All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”

The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.