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Sensitivity and area under the curve (AUC) analyses of thermography that is combined with diagnostic software demonstrate “the efficacy of the tool for breast cancer screening,” concludes an observational, comparative study from India published online Oct. 1 in JCO Global Oncology, a publication of the American Society of Clinical Oncology.

Siva Teja Kakileti of Niramai Health Analytix, Koramangala, Bangalore, India, and colleagues said that the product, Thermalytix, is potentially a good fit for low- and middle-income countries because it is portable and provides automated quantitative analysis of thermal images – and thus can be conducted by technicians with “minimal training.”

Conventional thermography involves manual interpretation of complex thermal images, which “often results in erroneous results owing to subjectivity,” said the study authors.

That manual interpretation of thermal images might involve looking at 200 color shades, which is “high cognitive overload for the thermographer,” explained Mr. Kakileti in an interview.

However, an American mammography expert who was approached for comment dismissed thermography – even with the new twist of software-aided diagnostic scoring by Thermalytix – as wholly inappropriate for the detection of early breast cancer, owing to inherent limitations.

“Thermal imaging of any type has no value in finding early breast cancer,” Daniel Kopans, MD, of Harvard University and Massachusetts General Hospital, both in Boston, said in an interview. He said that thermal imaging only detects heat on the skin and perhaps a few millimeters beneath the skin and thus misses deeper cancers, the heat from which is carried away by the vascular system.

The new study included 470 women who presented for breast screening at two centers in Bangalore, India. A total of 238 women had symptoms such as breast lump, nipple discharge, skin changes, or breast pain; the remaining 232 women were asymptomatic.

All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening (such as mammography, ultrasonography, biopsy, fine-needle aspiration, or elastography). A total of 78 women, or 16.6% of the group overall, were diagnosed with a malignancy. For the overall group of 470 women, Thermalytix had a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic,100%) and a specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall AUC of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women.

The study authors characterized both the sensitivity and AUC as “high.”

The results from the study, which the authors characterized as preliminary, encouraged the study sponsor, Niramai, to start planning a large-scale, multicountry trial.

But Dr. Kopans, who serves as a consultant to DART, which produces digital breast tomosynthesis units in China, suggested that this research will be fruitless. “Thermal imaging seems to raise its head every few years since it is passive, but it does not work and is a waste of money,” Dr. Kopans reiterated.

“Its use can be dangerous by dissuading women from being screened with mammography, which has been proven to save lives,” he stressed.
 

Thermalytix compared with mammography

Investigators also compared screening results in the subset of 242 women who underwent both Thermalytix and mammography. Results showed that Thermalytix had a higher sensitivity than did mammography (91.23% vs. 85.96%), but mammography had a higher specificity than Thermalytix did (94.05% vs. 68.65%).

In the asymptomatic group who underwent both tests (n = 95), four cancers were detected, and Thermalytix demonstrated superior sensitivity than mammography (100% vs. 50%), Mr. Kakileti and colleagues state.
 

Thermalytix evaluates vascularity variations too

In the subset of 228 women who did not undergo mammography (owing to dense breasts, younger age, or other reasons), Thermalytix detected tumors in all but 3 of 21 patients who went on to be diagnosed with breast cancer. The authors state that, because their artificial intelligence–based analysis uses vascularity, as well as temperature variations on the skin, to complement hot-spot detection, it is able to detect small lesions.

In the current study, 24 malignant tumors were less than 2 cm in diameter, and Thermalytix was able to identify 17 of the tumors as positive, for a 71% sensitivity rate for T1 tumors. This compared with a 68% sensitivity rate for mammography for detecting the same T1 tumors. Thermalytix also showed promising results in women younger than 40 years, for whom screening mammography is not usually recommended. The automated test picked up all 11 tumors eventually diagnosed in this younger cohort.

“Thermalytix is a portable, noninvasive, radiation-free test that has shown promising results in this preliminary study,” the investigators wrote, “[and] it can be an affordable and scalable method of screening in remote areas,” they added.

“We believe that Thermalytix ... is poised to be a promising modality for breast cancer screening,” Mr. Kakileti and colleagues summarized.
 

The FDA warns about thermography in place of mammography

The US Food and Drug Administration fairly recently warned against the use of thermography as an alternative to mammography for breast cancer screening or diagnosis, noting that it has received reports that facilities where thermography is offered often provide false information about the technology that can mislead patients into believing that it is either an alternative to or a better option than mammography.

Dr. Kopans says that other groups have invested in thermography research. “The Israelis spent millions working on a similar approach that didn’t work,” he commented.

The new software from Thermalytix, which is derived from artificial intelligence, is a “gimmick,” says the Boston radiologist. “If the basic information is not there, a computer cannot find it,” he stated, referring to what he believes are deeper-tissue tumors that are inaccessible to heat-detecting technology.

Mr. Kakileti is an employee of Nirami Health Analytix and owns stock and has filed patents with the company. Other investigators are also employed by the same company or receive research and other funding or have patents filed by the company as well. Dr. Kopans serves as a consultant to DART, which produces digital breast tomosynthesis units in China.
 

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

Sensitivity and area under the curve (AUC) analyses of thermography that is combined with diagnostic software demonstrate “the efficacy of the tool for breast cancer screening,” concludes an observational, comparative study from India published online Oct. 1 in JCO Global Oncology, a publication of the American Society of Clinical Oncology.

Siva Teja Kakileti of Niramai Health Analytix, Koramangala, Bangalore, India, and colleagues said that the product, Thermalytix, is potentially a good fit for low- and middle-income countries because it is portable and provides automated quantitative analysis of thermal images – and thus can be conducted by technicians with “minimal training.”

Conventional thermography involves manual interpretation of complex thermal images, which “often results in erroneous results owing to subjectivity,” said the study authors.

That manual interpretation of thermal images might involve looking at 200 color shades, which is “high cognitive overload for the thermographer,” explained Mr. Kakileti in an interview.

However, an American mammography expert who was approached for comment dismissed thermography – even with the new twist of software-aided diagnostic scoring by Thermalytix – as wholly inappropriate for the detection of early breast cancer, owing to inherent limitations.

“Thermal imaging of any type has no value in finding early breast cancer,” Daniel Kopans, MD, of Harvard University and Massachusetts General Hospital, both in Boston, said in an interview. He said that thermal imaging only detects heat on the skin and perhaps a few millimeters beneath the skin and thus misses deeper cancers, the heat from which is carried away by the vascular system.

The new study included 470 women who presented for breast screening at two centers in Bangalore, India. A total of 238 women had symptoms such as breast lump, nipple discharge, skin changes, or breast pain; the remaining 232 women were asymptomatic.

All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening (such as mammography, ultrasonography, biopsy, fine-needle aspiration, or elastography). A total of 78 women, or 16.6% of the group overall, were diagnosed with a malignancy. For the overall group of 470 women, Thermalytix had a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic,100%) and a specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall AUC of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women.

The study authors characterized both the sensitivity and AUC as “high.”

The results from the study, which the authors characterized as preliminary, encouraged the study sponsor, Niramai, to start planning a large-scale, multicountry trial.

But Dr. Kopans, who serves as a consultant to DART, which produces digital breast tomosynthesis units in China, suggested that this research will be fruitless. “Thermal imaging seems to raise its head every few years since it is passive, but it does not work and is a waste of money,” Dr. Kopans reiterated.

“Its use can be dangerous by dissuading women from being screened with mammography, which has been proven to save lives,” he stressed.
 

Thermalytix compared with mammography

Investigators also compared screening results in the subset of 242 women who underwent both Thermalytix and mammography. Results showed that Thermalytix had a higher sensitivity than did mammography (91.23% vs. 85.96%), but mammography had a higher specificity than Thermalytix did (94.05% vs. 68.65%).

In the asymptomatic group who underwent both tests (n = 95), four cancers were detected, and Thermalytix demonstrated superior sensitivity than mammography (100% vs. 50%), Mr. Kakileti and colleagues state.
 

Thermalytix evaluates vascularity variations too

In the subset of 228 women who did not undergo mammography (owing to dense breasts, younger age, or other reasons), Thermalytix detected tumors in all but 3 of 21 patients who went on to be diagnosed with breast cancer. The authors state that, because their artificial intelligence–based analysis uses vascularity, as well as temperature variations on the skin, to complement hot-spot detection, it is able to detect small lesions.

In the current study, 24 malignant tumors were less than 2 cm in diameter, and Thermalytix was able to identify 17 of the tumors as positive, for a 71% sensitivity rate for T1 tumors. This compared with a 68% sensitivity rate for mammography for detecting the same T1 tumors. Thermalytix also showed promising results in women younger than 40 years, for whom screening mammography is not usually recommended. The automated test picked up all 11 tumors eventually diagnosed in this younger cohort.

“Thermalytix is a portable, noninvasive, radiation-free test that has shown promising results in this preliminary study,” the investigators wrote, “[and] it can be an affordable and scalable method of screening in remote areas,” they added.

“We believe that Thermalytix ... is poised to be a promising modality for breast cancer screening,” Mr. Kakileti and colleagues summarized.
 

The FDA warns about thermography in place of mammography

The US Food and Drug Administration fairly recently warned against the use of thermography as an alternative to mammography for breast cancer screening or diagnosis, noting that it has received reports that facilities where thermography is offered often provide false information about the technology that can mislead patients into believing that it is either an alternative to or a better option than mammography.

Dr. Kopans says that other groups have invested in thermography research. “The Israelis spent millions working on a similar approach that didn’t work,” he commented.

The new software from Thermalytix, which is derived from artificial intelligence, is a “gimmick,” says the Boston radiologist. “If the basic information is not there, a computer cannot find it,” he stated, referring to what he believes are deeper-tissue tumors that are inaccessible to heat-detecting technology.

Mr. Kakileti is an employee of Nirami Health Analytix and owns stock and has filed patents with the company. Other investigators are also employed by the same company or receive research and other funding or have patents filed by the company as well. Dr. Kopans serves as a consultant to DART, which produces digital breast tomosynthesis units in China.
 

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

Sensitivity and area under the curve (AUC) analyses of thermography that is combined with diagnostic software demonstrate “the efficacy of the tool for breast cancer screening,” concludes an observational, comparative study from India published online Oct. 1 in JCO Global Oncology, a publication of the American Society of Clinical Oncology.

Siva Teja Kakileti of Niramai Health Analytix, Koramangala, Bangalore, India, and colleagues said that the product, Thermalytix, is potentially a good fit for low- and middle-income countries because it is portable and provides automated quantitative analysis of thermal images – and thus can be conducted by technicians with “minimal training.”

Conventional thermography involves manual interpretation of complex thermal images, which “often results in erroneous results owing to subjectivity,” said the study authors.

That manual interpretation of thermal images might involve looking at 200 color shades, which is “high cognitive overload for the thermographer,” explained Mr. Kakileti in an interview.

However, an American mammography expert who was approached for comment dismissed thermography – even with the new twist of software-aided diagnostic scoring by Thermalytix – as wholly inappropriate for the detection of early breast cancer, owing to inherent limitations.

“Thermal imaging of any type has no value in finding early breast cancer,” Daniel Kopans, MD, of Harvard University and Massachusetts General Hospital, both in Boston, said in an interview. He said that thermal imaging only detects heat on the skin and perhaps a few millimeters beneath the skin and thus misses deeper cancers, the heat from which is carried away by the vascular system.

The new study included 470 women who presented for breast screening at two centers in Bangalore, India. A total of 238 women had symptoms such as breast lump, nipple discharge, skin changes, or breast pain; the remaining 232 women were asymptomatic.

All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening (such as mammography, ultrasonography, biopsy, fine-needle aspiration, or elastography). A total of 78 women, or 16.6% of the group overall, were diagnosed with a malignancy. For the overall group of 470 women, Thermalytix had a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic,100%) and a specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall AUC of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women.

The study authors characterized both the sensitivity and AUC as “high.”

The results from the study, which the authors characterized as preliminary, encouraged the study sponsor, Niramai, to start planning a large-scale, multicountry trial.

But Dr. Kopans, who serves as a consultant to DART, which produces digital breast tomosynthesis units in China, suggested that this research will be fruitless. “Thermal imaging seems to raise its head every few years since it is passive, but it does not work and is a waste of money,” Dr. Kopans reiterated.

“Its use can be dangerous by dissuading women from being screened with mammography, which has been proven to save lives,” he stressed.
 

Thermalytix compared with mammography

Investigators also compared screening results in the subset of 242 women who underwent both Thermalytix and mammography. Results showed that Thermalytix had a higher sensitivity than did mammography (91.23% vs. 85.96%), but mammography had a higher specificity than Thermalytix did (94.05% vs. 68.65%).

In the asymptomatic group who underwent both tests (n = 95), four cancers were detected, and Thermalytix demonstrated superior sensitivity than mammography (100% vs. 50%), Mr. Kakileti and colleagues state.
 

Thermalytix evaluates vascularity variations too

In the subset of 228 women who did not undergo mammography (owing to dense breasts, younger age, or other reasons), Thermalytix detected tumors in all but 3 of 21 patients who went on to be diagnosed with breast cancer. The authors state that, because their artificial intelligence–based analysis uses vascularity, as well as temperature variations on the skin, to complement hot-spot detection, it is able to detect small lesions.

In the current study, 24 malignant tumors were less than 2 cm in diameter, and Thermalytix was able to identify 17 of the tumors as positive, for a 71% sensitivity rate for T1 tumors. This compared with a 68% sensitivity rate for mammography for detecting the same T1 tumors. Thermalytix also showed promising results in women younger than 40 years, for whom screening mammography is not usually recommended. The automated test picked up all 11 tumors eventually diagnosed in this younger cohort.

“Thermalytix is a portable, noninvasive, radiation-free test that has shown promising results in this preliminary study,” the investigators wrote, “[and] it can be an affordable and scalable method of screening in remote areas,” they added.

“We believe that Thermalytix ... is poised to be a promising modality for breast cancer screening,” Mr. Kakileti and colleagues summarized.
 

The FDA warns about thermography in place of mammography

The US Food and Drug Administration fairly recently warned against the use of thermography as an alternative to mammography for breast cancer screening or diagnosis, noting that it has received reports that facilities where thermography is offered often provide false information about the technology that can mislead patients into believing that it is either an alternative to or a better option than mammography.

Dr. Kopans says that other groups have invested in thermography research. “The Israelis spent millions working on a similar approach that didn’t work,” he commented.

The new software from Thermalytix, which is derived from artificial intelligence, is a “gimmick,” says the Boston radiologist. “If the basic information is not there, a computer cannot find it,” he stated, referring to what he believes are deeper-tissue tumors that are inaccessible to heat-detecting technology.

Mr. Kakileti is an employee of Nirami Health Analytix and owns stock and has filed patents with the company. Other investigators are also employed by the same company or receive research and other funding or have patents filed by the company as well. Dr. Kopans serves as a consultant to DART, which produces digital breast tomosynthesis units in China.
 

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

A novel urine-based assay improved detection of urothelial carcinoma when compared with conventional urine cytology in a prospective, observational study.

The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.

The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.

Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
 

Study details and results

The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.

The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.

In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.

Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.

UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.

“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”

The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
 

Conclusions and next steps

“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.

“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.

“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”

In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.

The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.

SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.

A novel urine-based assay improved detection of urothelial carcinoma when compared with conventional urine cytology in a prospective, observational study.

The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.

The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.

Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
 

Study details and results

The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.

The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.

In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.

Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.

UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.

“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”

The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
 

Conclusions and next steps

“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.

“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.

“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”

In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.

The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.

SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.

A novel urine-based assay improved detection of urothelial carcinoma when compared with conventional urine cytology in a prospective, observational study.

The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.

The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.

Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
 

Study details and results

The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.

The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.

In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.

Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.

UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.

“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”

The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
 

Conclusions and next steps

“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.

“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.

“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”

In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.

The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.

SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.

Acalabrutinib, a next-generation Bruton tyrosine kinase inhibitor, provides prolonged progression-free survival and better tolerability, compared with standard-of-care regimens for relapsed or refractory chronic lymphocytic leukemia (CLL), according to final results from the phase 3 ASCEND study.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

The estimated 18-month progression-free survival (PFS) at a median of 22 months was 82% in 155 patients treated with acalabrutinib, compared with 48% in 155 treated with investigator’s choice of either idelalisib-rituximab (IdR) or bendamustine-rituximab (BR), which were given in 119 and 36 patients, respectively, Paolo Ghia, MD, PhD, reported at the Society of Hematologic Oncology virtual meeting.

The benefits of acalabrutinib were apparent regardless of high-risk genetic characteristics: Those with and without both del(17p) and TP53 mutations had similarly good PFS outcomes with acalabrutinib versus IdR/BR (HRs, 0.11 and 0.29, respectively), as did those with versus without unmutated IgVH (HRs, 0.28 and 0.30, respectively), said Dr. Ghia, professor of medical oncology at the Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan.

The median overall survival was not reached in either arm, but estimated 18-month OS was 88% in both groups, likely because of the crossover being allowed for nonresponders in the IdR/BR groups, he noted.
 

Overall responses

The investigator-assessed overall response rates, including partial response or better, were also similar in the groups at 80% and 84%, respectively, and ORR, including partial response with lymphocytosis, was 92% versus 88%.

The duration of response was not reached in the acalabrutinib arm versus 18 months with IdR/BR, and estimated duration of response was 85% versus 49%.

The median drug exposure with acalabrutinib was approximately double that with IdR and about four times that of BR, Dr. Ghia said, noting that the difference between acalabrutinib and BR is explained by the short 6-month duration of treatment with BR, but the difference between acalabrutinib and IdR is because of adverse events (AEs).
 

Adverse events

AEs were the most common reason for treatment discontinuation in all three groups, but they led to discontinuation in only 16% with acalabrutinib versus 56% with IdR, he added.

The rates of AEs and AEs of clinical interest were generally similar to those reported at the interim analysis as presented in 2019 at the European Hematology Association annual meeting and published in the Journal of Clinical Oncology, despite the additional 6 months of follow up, he said.

Additionally, the incidence of grade 3 or higher AEs, serious AEs, and treatment-related AEs were all greater with IdR than with acalabrutinib or BR. The most common AEs with acalabrutinib were headache, neutropenia, diarrhea, and upper-respiratory infection, which were mostly grade 1 or 2. The most common grade 3 or higher AEs were neutropenia, anemia, and pneumonia, which were reported in 12%, 17%, and 7% of patients.
 

Confirmatory results

“The final results from the ASCEND study confirm the findings at the interim analysis and support the favorable efficacy and safety of acalabrutinib versus standard-of-care regimens ... in patients with relapsed/refractory CLL,” Dr. Ghia said.

“Overall, these final results from ASCENT support the use of acalabrutinib in patients with relapsed/refractory CLL, including those with high-risk genetic features.”

This study was sponsored by Acerta Pharma. Dr. Ghia reported consulting or advisory roles, grant or research funding, and/or honoraria from Abbvie, BeiGene, Janssen, Gilead Sciences, Sunesis Pharmaceuticals, Juno Therapeutics, ArQule, Adaptive Biotechnologies, Dynamo Therapeutics, MEI Pharma, and Novartis.

[email protected]

SOURCE: Ghia P et al. SOHO 2020, Abstract CLL-091.

Acalabrutinib, a next-generation Bruton tyrosine kinase inhibitor, provides prolonged progression-free survival and better tolerability, compared with standard-of-care regimens for relapsed or refractory chronic lymphocytic leukemia (CLL), according to final results from the phase 3 ASCEND study.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

The estimated 18-month progression-free survival (PFS) at a median of 22 months was 82% in 155 patients treated with acalabrutinib, compared with 48% in 155 treated with investigator’s choice of either idelalisib-rituximab (IdR) or bendamustine-rituximab (BR), which were given in 119 and 36 patients, respectively, Paolo Ghia, MD, PhD, reported at the Society of Hematologic Oncology virtual meeting.

The benefits of acalabrutinib were apparent regardless of high-risk genetic characteristics: Those with and without both del(17p) and TP53 mutations had similarly good PFS outcomes with acalabrutinib versus IdR/BR (HRs, 0.11 and 0.29, respectively), as did those with versus without unmutated IgVH (HRs, 0.28 and 0.30, respectively), said Dr. Ghia, professor of medical oncology at the Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan.

The median overall survival was not reached in either arm, but estimated 18-month OS was 88% in both groups, likely because of the crossover being allowed for nonresponders in the IdR/BR groups, he noted.
 

Overall responses

The investigator-assessed overall response rates, including partial response or better, were also similar in the groups at 80% and 84%, respectively, and ORR, including partial response with lymphocytosis, was 92% versus 88%.

The duration of response was not reached in the acalabrutinib arm versus 18 months with IdR/BR, and estimated duration of response was 85% versus 49%.

The median drug exposure with acalabrutinib was approximately double that with IdR and about four times that of BR, Dr. Ghia said, noting that the difference between acalabrutinib and BR is explained by the short 6-month duration of treatment with BR, but the difference between acalabrutinib and IdR is because of adverse events (AEs).
 

Adverse events

AEs were the most common reason for treatment discontinuation in all three groups, but they led to discontinuation in only 16% with acalabrutinib versus 56% with IdR, he added.

The rates of AEs and AEs of clinical interest were generally similar to those reported at the interim analysis as presented in 2019 at the European Hematology Association annual meeting and published in the Journal of Clinical Oncology, despite the additional 6 months of follow up, he said.

Additionally, the incidence of grade 3 or higher AEs, serious AEs, and treatment-related AEs were all greater with IdR than with acalabrutinib or BR. The most common AEs with acalabrutinib were headache, neutropenia, diarrhea, and upper-respiratory infection, which were mostly grade 1 or 2. The most common grade 3 or higher AEs were neutropenia, anemia, and pneumonia, which were reported in 12%, 17%, and 7% of patients.
 

Confirmatory results

“The final results from the ASCEND study confirm the findings at the interim analysis and support the favorable efficacy and safety of acalabrutinib versus standard-of-care regimens ... in patients with relapsed/refractory CLL,” Dr. Ghia said.

“Overall, these final results from ASCENT support the use of acalabrutinib in patients with relapsed/refractory CLL, including those with high-risk genetic features.”

This study was sponsored by Acerta Pharma. Dr. Ghia reported consulting or advisory roles, grant or research funding, and/or honoraria from Abbvie, BeiGene, Janssen, Gilead Sciences, Sunesis Pharmaceuticals, Juno Therapeutics, ArQule, Adaptive Biotechnologies, Dynamo Therapeutics, MEI Pharma, and Novartis.

[email protected]

SOURCE: Ghia P et al. SOHO 2020, Abstract CLL-091.

Acalabrutinib, a next-generation Bruton tyrosine kinase inhibitor, provides prolonged progression-free survival and better tolerability, compared with standard-of-care regimens for relapsed or refractory chronic lymphocytic leukemia (CLL), according to final results from the phase 3 ASCEND study.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

The estimated 18-month progression-free survival (PFS) at a median of 22 months was 82% in 155 patients treated with acalabrutinib, compared with 48% in 155 treated with investigator’s choice of either idelalisib-rituximab (IdR) or bendamustine-rituximab (BR), which were given in 119 and 36 patients, respectively, Paolo Ghia, MD, PhD, reported at the Society of Hematologic Oncology virtual meeting.

The benefits of acalabrutinib were apparent regardless of high-risk genetic characteristics: Those with and without both del(17p) and TP53 mutations had similarly good PFS outcomes with acalabrutinib versus IdR/BR (HRs, 0.11 and 0.29, respectively), as did those with versus without unmutated IgVH (HRs, 0.28 and 0.30, respectively), said Dr. Ghia, professor of medical oncology at the Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan.

The median overall survival was not reached in either arm, but estimated 18-month OS was 88% in both groups, likely because of the crossover being allowed for nonresponders in the IdR/BR groups, he noted.
 

Overall responses

The investigator-assessed overall response rates, including partial response or better, were also similar in the groups at 80% and 84%, respectively, and ORR, including partial response with lymphocytosis, was 92% versus 88%.

The duration of response was not reached in the acalabrutinib arm versus 18 months with IdR/BR, and estimated duration of response was 85% versus 49%.

The median drug exposure with acalabrutinib was approximately double that with IdR and about four times that of BR, Dr. Ghia said, noting that the difference between acalabrutinib and BR is explained by the short 6-month duration of treatment with BR, but the difference between acalabrutinib and IdR is because of adverse events (AEs).
 

Adverse events

AEs were the most common reason for treatment discontinuation in all three groups, but they led to discontinuation in only 16% with acalabrutinib versus 56% with IdR, he added.

The rates of AEs and AEs of clinical interest were generally similar to those reported at the interim analysis as presented in 2019 at the European Hematology Association annual meeting and published in the Journal of Clinical Oncology, despite the additional 6 months of follow up, he said.

Additionally, the incidence of grade 3 or higher AEs, serious AEs, and treatment-related AEs were all greater with IdR than with acalabrutinib or BR. The most common AEs with acalabrutinib were headache, neutropenia, diarrhea, and upper-respiratory infection, which were mostly grade 1 or 2. The most common grade 3 or higher AEs were neutropenia, anemia, and pneumonia, which were reported in 12%, 17%, and 7% of patients.
 

Confirmatory results

“The final results from the ASCEND study confirm the findings at the interim analysis and support the favorable efficacy and safety of acalabrutinib versus standard-of-care regimens ... in patients with relapsed/refractory CLL,” Dr. Ghia said.

“Overall, these final results from ASCENT support the use of acalabrutinib in patients with relapsed/refractory CLL, including those with high-risk genetic features.”

This study was sponsored by Acerta Pharma. Dr. Ghia reported consulting or advisory roles, grant or research funding, and/or honoraria from Abbvie, BeiGene, Janssen, Gilead Sciences, Sunesis Pharmaceuticals, Juno Therapeutics, ArQule, Adaptive Biotechnologies, Dynamo Therapeutics, MEI Pharma, and Novartis.

[email protected]

SOURCE: Ghia P et al. SOHO 2020, Abstract CLL-091.

An updated European Society for Medical Oncology (ESMO) clinical practice guidelines were released to provide key recommendations on the management of chronic lymphocytic leukemia (CLL).

The guidelines were developed by a multidisciplinary group of experts from different institutions and countries in Europe and provide levels of evidence and grades of recommendation where applicable for issues regarding prognosis and treatment decisions in CLL. Such decisions depend on genetic and clinical factors such as age, stage, and comorbidities. The guidelines also focus on new therapies targeting B-cell-receptor pathways or defect mechanism of apoptosis, which have been found to induce long-lasting remissions. The guidelines were endorsed by the European Hematology Association (EHA) through the Scientific Working Group on CLL/European Research Initiative on CLL (ERIC), according to the report published online the Annals of Oncology.

These clinical practice guidelines were developed in accordance with the ESMO standard operating procedures for clinical practice guidelines development with use of relevant literature selected by the expert authors. Statements without grading were considered justified as standard clinical practice by the experts and the ESMO faculty.

Below are some highlights of the guidelines, which cover a wide array of topics regarding the diagnosis, staging, treatment, and progression of CLL disease.
 

Diagnosis

The guidelines indicate that CLL diagnosis is usually possible by immunophenotyping of peripheral blood only and that lymph node (LN) biopsy and/or bone marrow biopsy may be helpful if immunophenotyping is not conclusive for the diagnosis of CLL, according to Barbara Eichhorst, MD, of the University of Cologne (Germany) and colleagues on behalf of the ESMO guidelines committee.

Staging and risk assessment

Early asymptomatic-stage disease does not need further risk assessment, but after the first year, when all patients should be seen at 3-monthly intervals, patients can be followed every 3-12 months. The interval would depend on burden and dynamics of the disease obtained by the using history and physical examinations, including a careful palpation of all LN areas, spleen, and liver, as well as assessing complete blood cell count and differential count, according to the report.

Advanced- and symptomatic-stage disease requires a broader examination including imaging, history and status of relevant infections, and fluorescent in situ hybridization (FISH) assays for the detection of deletion of the chromosome 17 (del[17p]) affecting the tumor protein p53 expression and, in the absence of del(17p), TP53 sequencing for detection of TP53 gene mutation, according to the authors.

Prognostication

Two clinical staging systems are typically used in CLL. Both Binet and Rai staging systems separate three groups of patients with different prognosis, although “as a consequence of more effective therapy, the overall survival (OS) of patients with advanced stage has improved and the relevance of the staging systems for prognostication has decreased,” according to the report.

The recent addition of genetic markers has also proved highly relevant to identifying patients with different prognoses and to guide treatment.
 

Therapy

Although CLL is an incurable disease, choice and application of treatment are strongly tied to the length of survival, according to the authors. The guidelines recommend Binet and Rai staging with clinical symptoms as relevant for treatment indication. In addition, the identification of del(17p), TP53 mutations, and IGHV status are relevant for choice of therapy and should be assessed prior to treatment.

The guidelines discuss specific treatment modalities for various stages of the disease, from early stages to relapse.

For frontline therapy, different treatment strategies are available including continuous treatment with Bruton tyrosine kinase (BTK)–inhibitors, such as ibrutinib, until progression or time-limited therapy with ChT backbone and CD20 antibodies. In addition, the Food and Drug Administration and European Medicines Agency have recently approved the combination of venetoclax plus obinutuzumab for first-line therapy of CLL.

Treatment decisions should include an assessment of IGHV and TP53 status, as well as patient-related factors such as comedication, comorbidities, preferences, drug availability, and potential of treatment adherence, according to the guidelines.

In case of symptomatic relapse within 3 years after fixed-duration therapy or nonresponse to therapy, the guidelines recommend that the therapeutic regimen should be changed, regardless of the type of first-line either to venetoclax plus rituximab for 24 months or to ibrutinib, acalabrutinib, or other BTK inhibitors (if available) as continuous therapy.

The guidelines also discuss the possible roles for hematopoietic stem cell transplantation and cellular therapies, as well as the treatment of the various complications that can arise in patients with CLL, and dealing with various aspects of disease progression.

No external funds were provided for the production of the guidelines. The authors of the report and members of the ESMO Guidelines Committee reported numerous disclosures regarding pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Eichhorst B et al. Ann Oncol. 2020 Oct 19. doi: 10.1016/j.annonc.2020.09.019.

An updated European Society for Medical Oncology (ESMO) clinical practice guidelines were released to provide key recommendations on the management of chronic lymphocytic leukemia (CLL).

The guidelines were developed by a multidisciplinary group of experts from different institutions and countries in Europe and provide levels of evidence and grades of recommendation where applicable for issues regarding prognosis and treatment decisions in CLL. Such decisions depend on genetic and clinical factors such as age, stage, and comorbidities. The guidelines also focus on new therapies targeting B-cell-receptor pathways or defect mechanism of apoptosis, which have been found to induce long-lasting remissions. The guidelines were endorsed by the European Hematology Association (EHA) through the Scientific Working Group on CLL/European Research Initiative on CLL (ERIC), according to the report published online the Annals of Oncology.

These clinical practice guidelines were developed in accordance with the ESMO standard operating procedures for clinical practice guidelines development with use of relevant literature selected by the expert authors. Statements without grading were considered justified as standard clinical practice by the experts and the ESMO faculty.

Below are some highlights of the guidelines, which cover a wide array of topics regarding the diagnosis, staging, treatment, and progression of CLL disease.
 

Diagnosis

The guidelines indicate that CLL diagnosis is usually possible by immunophenotyping of peripheral blood only and that lymph node (LN) biopsy and/or bone marrow biopsy may be helpful if immunophenotyping is not conclusive for the diagnosis of CLL, according to Barbara Eichhorst, MD, of the University of Cologne (Germany) and colleagues on behalf of the ESMO guidelines committee.

Staging and risk assessment

Early asymptomatic-stage disease does not need further risk assessment, but after the first year, when all patients should be seen at 3-monthly intervals, patients can be followed every 3-12 months. The interval would depend on burden and dynamics of the disease obtained by the using history and physical examinations, including a careful palpation of all LN areas, spleen, and liver, as well as assessing complete blood cell count and differential count, according to the report.

Advanced- and symptomatic-stage disease requires a broader examination including imaging, history and status of relevant infections, and fluorescent in situ hybridization (FISH) assays for the detection of deletion of the chromosome 17 (del[17p]) affecting the tumor protein p53 expression and, in the absence of del(17p), TP53 sequencing for detection of TP53 gene mutation, according to the authors.

Prognostication

Two clinical staging systems are typically used in CLL. Both Binet and Rai staging systems separate three groups of patients with different prognosis, although “as a consequence of more effective therapy, the overall survival (OS) of patients with advanced stage has improved and the relevance of the staging systems for prognostication has decreased,” according to the report.

The recent addition of genetic markers has also proved highly relevant to identifying patients with different prognoses and to guide treatment.
 

Therapy

Although CLL is an incurable disease, choice and application of treatment are strongly tied to the length of survival, according to the authors. The guidelines recommend Binet and Rai staging with clinical symptoms as relevant for treatment indication. In addition, the identification of del(17p), TP53 mutations, and IGHV status are relevant for choice of therapy and should be assessed prior to treatment.

The guidelines discuss specific treatment modalities for various stages of the disease, from early stages to relapse.

For frontline therapy, different treatment strategies are available including continuous treatment with Bruton tyrosine kinase (BTK)–inhibitors, such as ibrutinib, until progression or time-limited therapy with ChT backbone and CD20 antibodies. In addition, the Food and Drug Administration and European Medicines Agency have recently approved the combination of venetoclax plus obinutuzumab for first-line therapy of CLL.

Treatment decisions should include an assessment of IGHV and TP53 status, as well as patient-related factors such as comedication, comorbidities, preferences, drug availability, and potential of treatment adherence, according to the guidelines.

In case of symptomatic relapse within 3 years after fixed-duration therapy or nonresponse to therapy, the guidelines recommend that the therapeutic regimen should be changed, regardless of the type of first-line either to venetoclax plus rituximab for 24 months or to ibrutinib, acalabrutinib, or other BTK inhibitors (if available) as continuous therapy.

The guidelines also discuss the possible roles for hematopoietic stem cell transplantation and cellular therapies, as well as the treatment of the various complications that can arise in patients with CLL, and dealing with various aspects of disease progression.

No external funds were provided for the production of the guidelines. The authors of the report and members of the ESMO Guidelines Committee reported numerous disclosures regarding pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Eichhorst B et al. Ann Oncol. 2020 Oct 19. doi: 10.1016/j.annonc.2020.09.019.

An updated European Society for Medical Oncology (ESMO) clinical practice guidelines were released to provide key recommendations on the management of chronic lymphocytic leukemia (CLL).

The guidelines were developed by a multidisciplinary group of experts from different institutions and countries in Europe and provide levels of evidence and grades of recommendation where applicable for issues regarding prognosis and treatment decisions in CLL. Such decisions depend on genetic and clinical factors such as age, stage, and comorbidities. The guidelines also focus on new therapies targeting B-cell-receptor pathways or defect mechanism of apoptosis, which have been found to induce long-lasting remissions. The guidelines were endorsed by the European Hematology Association (EHA) through the Scientific Working Group on CLL/European Research Initiative on CLL (ERIC), according to the report published online the Annals of Oncology.

These clinical practice guidelines were developed in accordance with the ESMO standard operating procedures for clinical practice guidelines development with use of relevant literature selected by the expert authors. Statements without grading were considered justified as standard clinical practice by the experts and the ESMO faculty.

Below are some highlights of the guidelines, which cover a wide array of topics regarding the diagnosis, staging, treatment, and progression of CLL disease.
 

Diagnosis

The guidelines indicate that CLL diagnosis is usually possible by immunophenotyping of peripheral blood only and that lymph node (LN) biopsy and/or bone marrow biopsy may be helpful if immunophenotyping is not conclusive for the diagnosis of CLL, according to Barbara Eichhorst, MD, of the University of Cologne (Germany) and colleagues on behalf of the ESMO guidelines committee.

Staging and risk assessment

Early asymptomatic-stage disease does not need further risk assessment, but after the first year, when all patients should be seen at 3-monthly intervals, patients can be followed every 3-12 months. The interval would depend on burden and dynamics of the disease obtained by the using history and physical examinations, including a careful palpation of all LN areas, spleen, and liver, as well as assessing complete blood cell count and differential count, according to the report.

Advanced- and symptomatic-stage disease requires a broader examination including imaging, history and status of relevant infections, and fluorescent in situ hybridization (FISH) assays for the detection of deletion of the chromosome 17 (del[17p]) affecting the tumor protein p53 expression and, in the absence of del(17p), TP53 sequencing for detection of TP53 gene mutation, according to the authors.

Prognostication

Two clinical staging systems are typically used in CLL. Both Binet and Rai staging systems separate three groups of patients with different prognosis, although “as a consequence of more effective therapy, the overall survival (OS) of patients with advanced stage has improved and the relevance of the staging systems for prognostication has decreased,” according to the report.

The recent addition of genetic markers has also proved highly relevant to identifying patients with different prognoses and to guide treatment.
 

Therapy

Although CLL is an incurable disease, choice and application of treatment are strongly tied to the length of survival, according to the authors. The guidelines recommend Binet and Rai staging with clinical symptoms as relevant for treatment indication. In addition, the identification of del(17p), TP53 mutations, and IGHV status are relevant for choice of therapy and should be assessed prior to treatment.

The guidelines discuss specific treatment modalities for various stages of the disease, from early stages to relapse.

For frontline therapy, different treatment strategies are available including continuous treatment with Bruton tyrosine kinase (BTK)–inhibitors, such as ibrutinib, until progression or time-limited therapy with ChT backbone and CD20 antibodies. In addition, the Food and Drug Administration and European Medicines Agency have recently approved the combination of venetoclax plus obinutuzumab for first-line therapy of CLL.

Treatment decisions should include an assessment of IGHV and TP53 status, as well as patient-related factors such as comedication, comorbidities, preferences, drug availability, and potential of treatment adherence, according to the guidelines.

In case of symptomatic relapse within 3 years after fixed-duration therapy or nonresponse to therapy, the guidelines recommend that the therapeutic regimen should be changed, regardless of the type of first-line either to venetoclax plus rituximab for 24 months or to ibrutinib, acalabrutinib, or other BTK inhibitors (if available) as continuous therapy.

The guidelines also discuss the possible roles for hematopoietic stem cell transplantation and cellular therapies, as well as the treatment of the various complications that can arise in patients with CLL, and dealing with various aspects of disease progression.

No external funds were provided for the production of the guidelines. The authors of the report and members of the ESMO Guidelines Committee reported numerous disclosures regarding pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Eichhorst B et al. Ann Oncol. 2020 Oct 19. doi: 10.1016/j.annonc.2020.09.019.

How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.

“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.

As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”

Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”

Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”

Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.

OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.

His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).

Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”

How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”

However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.

SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.

“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.

As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”

Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”

Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”

Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.

OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.

His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).

Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”

How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”

However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.

SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.

“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.

As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”

Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”

Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”

Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.

OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.

His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).

Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”

How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”

However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.

SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.

CoRus13/Wikimedia Commons/Creative Commons 4.0

Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.

These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.

The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
 

Promising results for many

There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.

With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.

The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).

Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.

“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.

The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.

[email protected]

SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.

Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.

CoRus13/Wikimedia Commons/Creative Commons 4.0

Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.

These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.

The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
 

Promising results for many

There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.

With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.

The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).

Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.

“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.

The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.

[email protected]

SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.

Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.

CoRus13/Wikimedia Commons/Creative Commons 4.0

Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.

These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.

The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
 

Promising results for many

There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.

With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.

The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).

Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.

“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.

The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.

[email protected]

SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.

When the first reports emerged of “cytokine storm” in patients with severe COVID-19, all eyes turned to cancer research. Oncologists have years of experience reigning in “cytokine release syndrome” (CRS) in patients treated with chimeric antigen receptor (CAR) therapies for advanced blood cancers.

There was hope that drugs used to quell CRS in patients with cancer would be effective in patients with severe COVID. But the promise of a quick fix with oncology medications has yet to be fully realized.

Part of the problem is that the two conditions, while analogous, are “not the same,” said Nirali Shah, MD, head of the hematologic malignancies section in the pediatric oncology branch at the National Cancer Institute.

“You have to understand the underlying pathophysiology, what triggers the inflammation,” Dr. Shah said.

CAR T–related CRS is caused by activated T cells in patients with cancer who often do not have an infection, she explained. In contrast, cytokine storm in COVID-19 is triggered by a viral pathogen that can drive “out of control” inflammation. These differences may explain why drugs work in the first instance, but not in the second, she added. Drugs that inhibit interleukin-6 (such as tocilizumab, sarilumab, and siltuximab) are used with great success to dampen down the CRS in patients receiving CAR therapy for blood cancers. And although trials of these agents in patients with COVID are still ongoing, initial results are disappointing.

The first global, phase 3 randomized controlled trial of tocilizumab in severe COVID-19 failed to meet its primary endpoint of improved clinical status, and it did not meet its secondary endpoint of improved mortality at week 4.

In its recent recommendations, the National Institutes of Health noted a lack of data to support the efficacy of IL-6 inhibitors in COVID-19, and recommended against their use, except as part of a clinical trial.
 

Trimming the tree vs. cutting it down

As researchers have begun to decode the immune process underlying severe COVID-19, they have turned to other cancer drugs to tame cytokine storm.

Louis Staudt, MD, PhD, and Wyndham Wilson, MD, PhD, both at the NCI, think that cytokine storm in COVID-19 is driven by macrophages, which trigger release of multiple cytokines.

For years, the pair have been studying lymphoid tumors. Dr. Staudt is chief of the lymphoid malignancies branch at the NCI, and Wilson is head of the lymphoma therapeutics section. In past work, Dr. Staudt discovered that inhibiting an enzyme called bruton tyrosine kinase (BTK) dampens macrophage function.

When the pandemic began, Dr. Staudt and Dr. Wilson realized that singling out just one cytokine like IL-6 may not be enough. They thought that a more effective approach may be to target macrophages with a BTK inhibitor called acalabrutinib (Calquence), which would inhibit multiple cytokines at the same time.

Dr. Staudt likens the immune response to a tree, with the macrophages composing the tree trunk and the limbs made up of individual cytokines.

“Targeting macrophages is getting at the trunk of the problem,” he said. “You’re only cutting off the limbs with tocilizumab.”

In just 3 days, Dr. Staudt and Dr. Wilson went from concept to approval to launching a prospective, observational study. The study took place at five centers in the US, and included 19 patients hospitalized with COVID-19; the results were published in Science Immunology. Over a treatment course of 14 days, the majority of patients treated off-label with acalabrutinib improved, some within 24 hours. Eight of 11 patients on supplemental oxygen were discharged on room air. Four of eight patients on ventilators were extubated, with two of these discharged on room air. Two patients on ventilators died. No discernible toxicity was noted.

Analyses also showed increased BTK activity and elevated IL-6 levels in monocytes – precursors of macrophages – in patients with severe COVID-19, compared with healthy volunteers.

“We showed that the target of acalabrutinib was active in the immune cells of patients with severe COVID-19,” Dr. Staudt said. “So we have the target. We have the drug to hit the target. And we have an apparent clinical benefit.”

Those three things were compelling enough to launch the CALAVI phase 2 trial, an open-label, randomized, controlled trial, sponsored by AstraZeneca and the NCI, that is being conducted in the United States and internationally. It is testing acalabrutinib with best supportive care versus BSC alone in people hospitalized with COVID-19. The trial is scheduled to be completed on Nov. 26.

Preliminary insights from this trial are expected soon. “These are not insights that we will likely publish, but they are important insights that will lead to the launch of a definitive double-blind, randomized, phase 3 trial, which we hope to launch in the next month or so,” Dr. Wilson said.
 

Targeting inflammation and infection simultaneously

Other scientists are investigating inhibitors of Janus kinase (JAK), a family of enzymes that play a key role in orchestrating immune responses, particularly cytokines. Interest in JAK inhibition to control hyperinflammation in cancer goes back at least 15 years, and drugs that act as JAK inhibitors are already approved for use in the treatment of myelofibrosis (ruxolitinib [Jakafi], fedratinib [Inrebic]) and also for rheumatoid arthritis (upadacitinib [Rinvoq], baricitinib [Olumiant]).

“It wasn’t a huge leap for those of us with a lot of understanding of JAK inhibitors to propose taking them into the clinic to treat patients with COVID-19,” commented John Mascarenhas, MD, the leader of clinical investigation in the myeloproliferative disorders program at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Mascarenhas is also principal investigator of the PRE-VENT trial, which is comparing the investigational JAK2 inhibitor pacritinib plus standard of care to standard of care alone in patients hospitalized with severe COVID-19, with and without cancer. The trial is sponsored by CTI BioPharma (manufacturer of pacritinib), and is taking place at 10 sites in the United States.

In a move that may raise eyebrows, PRE-VENT skipped phase 1 and 2 and went straight to phase 3. Pacritinib has yet to receive FDA approval and has mostly been studied in myelofibrosis, an intensely inflammatory disease.

The decision was based on trials of pacritinib in hematologic malignancies and also on results from a phase 2 study in China that found possible clinical benefit for the JAK 1/2 inhibitor ruxolitinib in 43 patients hospitalized with severe COVID-19, although results were not statistically significant, Dr. Mascarenhas explained.

Recent results from Lilly’s ACTT-2 study have provided further support for the role of JAK inhibitors in treating cytokine storm. ACTT-2 is a phase 3, double-blind, placebo-controlled, randomized, controlled trial sponsored by the NIH and NIAID comparing the JAK 1/2 inhibitor baricitinib plus the antiviral remdesivir with remdesivir alone in patients hospitalized with COVID-19. In September, Lilly announced that the trial met its primary endpoint of decreased time to recovery in patients who received baricitinib in combination with remdesivir.

But pacritinib’s mechanism of action may take things a step further. The drug selectively inhibits JAK2 and spares JAK1, which is important for antiviral activity in the immune system. Also, in vitro data suggests pacritinib may simultaneously reduce inflammation and fight off the virus by selectively inhibiting two additional enzymes and two other receptors.

“The rationale to me is very strong for using pacritinib,” Dr. Mascarenhas said. “I think this approach was bold but appropriate.”

The main safety concern with pacritinib could be bleeding, especially among patients on anticoagulants, Dr. Mascarenhas said. Because some patients with severe COVID-19 tend to develop blood clots, anticoagulation has become the standard of care at many institutions.

Because the trial is just beginning – only a minority of the total planned population of 358 patients has been enrolled – no interim results are available.
 

Right drug, wrong time?

IL-6 inhibition could still have a role to play in COVID-19, but the trick could be in the timing. Most of the trials so far have studied tocilizumab in patients with severe COVID-19, many of whom were already on ventilators. At that point, it may be too late to reverse the damage that has already taken place.

One of the main reasons tocilizumab works so well in CRS after CAR T therapy is that oncologists have learned how to use it early, often within 24 hours of fever onset. Oncologists use the American Society for Transplantation and Cellular Therapy consensus grading system, which helps them identify CRS when it is easier to control.

But applying the ASTCT grading system to COVID-19 is problematic. “Almost by definition, patients hospitalized with COVID-19 have low oxygen levels, which throws off the scale,” said Joshua Hill, MD, an infectious disease specialist at Fred Hutchinson Cancer Research Center in Seattle, who has research expertise in infectious complications after CAR T therapy.

“The key is to intervene earlier to prevent damage to the lungs and other end organs. We don’t have anything magical that will reverse that damage,” Dr. Hill said.

Results from the phase 3 trial EMPACTA trial (sponsored by Genentech) seem to bear this out. EMPACTA is evaluating use of tocilizumab in hospitalized patients with less severe COVID-19 who do not yet require mechanical ventilation. The trial is notable for being the first global phase 3 trial to demonstrate efficacy for tocilizumab vs placebo in hospitalized patients with COVID-19 pneumonia, and for including a high percentage of racial/ethnic minorities (85% of 389 participants), who have been hard hit by the pandemic and have historically been underrepresented in drug trials.

Last month, Roche announced that EMPACTA met its primary endpoint. Results showed that patients hospitalized with COVID-19 pneumonia who received tocilizumab plus standard of care were 44% less likely to go on mechanical ventilation or die, compared with those who received placebo plus standard of care (P = .0348), although there were no statistically significant differences in death by day 28 between tocilizumab and placebo (10.4% vs. 8.6%, P = .5146).

However, earlier administration of tocilizumab raises another issue. IL-6 and its pathway are important for clearing viral infections. Using tocilizumab in the context of an ongoing infection could raise safety issues.

Also, tocilizumab sticks around in the body for a relatively long time. In the treatment of rheumatoid arthritis, it is dosed once a month, and it carries a black box warning for reactivation of tuberculosis.

Whereas results from EMPACTA showed similar rates of infection associated with tocilizumab and placebo (10% vs. 11%), at least one other study has found increased rates of superinfection in patients with severe COVID-19 who received tocilizumab. Overall, though, the drug was associated with decreased risk of death in the latter study.

A phase 2 trial called COVIDOSE is tackling the safety issue. COVIDOSE is evaluating whether low-dose tocilizumab is effective in noncritical COVID-19 patients, with the idea that lower doses could be safer. Early results published as a preprint before peer review indicated that low-dose tocilizumab (ranging from 40 mg to 200 mg) was associated with clinical improvement in 32 noncritical patients hospitalized with COVID-19.

Five patients (15.6%) developed bacterial superinfections, and five (15.6%) died by 28-day follow-up, although there wasn’t a perfect “overlap” between these groups of patients. Bacterial superinfection was not the cause of death in all five patients who died, and not all patients who died developed bacterial superinfections, according to senior author Pankti Reid, MD, MPH, an assistant professor of medicine at the University of Chicago.

Results from COVIDOSE also showed that treatment with tocilizumab did not seem to affect the ability of patients to develop antibodies against COVID-19. The results set the stage for a larger randomized, controlled trial (still ongoing) to determine the optimal dose of tocilizumab.

Still, Dr. Hill urges caution.

Many of these immunomodulators have been used only in the context of a clinical trial, or only for patients with terminal cancer and no other treatment options. In patients with cancer, these drugs have been studied and have shown an “acceptable safety profile,” according to Dr. Shah.

But this is a different situation, and when it comes to repurposing them to relatively healthy patients with COVID-19, Dr. Hill emphasized the need for careful research.

“We’re always very concerned about giving drugs that suppress the immune response if people have active infections,” Dr. Hill said. “Often times we think it makes things worse, and it typically does.”

Dr. Mascarenhas reported institutional research funding from CTI Biopharma. Dr. Hill, Dr. Staudt, Dr. Wilson, and Dr. Shah disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

When the first reports emerged of “cytokine storm” in patients with severe COVID-19, all eyes turned to cancer research. Oncologists have years of experience reigning in “cytokine release syndrome” (CRS) in patients treated with chimeric antigen receptor (CAR) therapies for advanced blood cancers.

There was hope that drugs used to quell CRS in patients with cancer would be effective in patients with severe COVID. But the promise of a quick fix with oncology medications has yet to be fully realized.

Part of the problem is that the two conditions, while analogous, are “not the same,” said Nirali Shah, MD, head of the hematologic malignancies section in the pediatric oncology branch at the National Cancer Institute.

“You have to understand the underlying pathophysiology, what triggers the inflammation,” Dr. Shah said.

CAR T–related CRS is caused by activated T cells in patients with cancer who often do not have an infection, she explained. In contrast, cytokine storm in COVID-19 is triggered by a viral pathogen that can drive “out of control” inflammation. These differences may explain why drugs work in the first instance, but not in the second, she added. Drugs that inhibit interleukin-6 (such as tocilizumab, sarilumab, and siltuximab) are used with great success to dampen down the CRS in patients receiving CAR therapy for blood cancers. And although trials of these agents in patients with COVID are still ongoing, initial results are disappointing.

The first global, phase 3 randomized controlled trial of tocilizumab in severe COVID-19 failed to meet its primary endpoint of improved clinical status, and it did not meet its secondary endpoint of improved mortality at week 4.

In its recent recommendations, the National Institutes of Health noted a lack of data to support the efficacy of IL-6 inhibitors in COVID-19, and recommended against their use, except as part of a clinical trial.
 

Trimming the tree vs. cutting it down

As researchers have begun to decode the immune process underlying severe COVID-19, they have turned to other cancer drugs to tame cytokine storm.

Louis Staudt, MD, PhD, and Wyndham Wilson, MD, PhD, both at the NCI, think that cytokine storm in COVID-19 is driven by macrophages, which trigger release of multiple cytokines.

For years, the pair have been studying lymphoid tumors. Dr. Staudt is chief of the lymphoid malignancies branch at the NCI, and Wilson is head of the lymphoma therapeutics section. In past work, Dr. Staudt discovered that inhibiting an enzyme called bruton tyrosine kinase (BTK) dampens macrophage function.

When the pandemic began, Dr. Staudt and Dr. Wilson realized that singling out just one cytokine like IL-6 may not be enough. They thought that a more effective approach may be to target macrophages with a BTK inhibitor called acalabrutinib (Calquence), which would inhibit multiple cytokines at the same time.

Dr. Staudt likens the immune response to a tree, with the macrophages composing the tree trunk and the limbs made up of individual cytokines.

“Targeting macrophages is getting at the trunk of the problem,” he said. “You’re only cutting off the limbs with tocilizumab.”

In just 3 days, Dr. Staudt and Dr. Wilson went from concept to approval to launching a prospective, observational study. The study took place at five centers in the US, and included 19 patients hospitalized with COVID-19; the results were published in Science Immunology. Over a treatment course of 14 days, the majority of patients treated off-label with acalabrutinib improved, some within 24 hours. Eight of 11 patients on supplemental oxygen were discharged on room air. Four of eight patients on ventilators were extubated, with two of these discharged on room air. Two patients on ventilators died. No discernible toxicity was noted.

Analyses also showed increased BTK activity and elevated IL-6 levels in monocytes – precursors of macrophages – in patients with severe COVID-19, compared with healthy volunteers.

“We showed that the target of acalabrutinib was active in the immune cells of patients with severe COVID-19,” Dr. Staudt said. “So we have the target. We have the drug to hit the target. And we have an apparent clinical benefit.”

Those three things were compelling enough to launch the CALAVI phase 2 trial, an open-label, randomized, controlled trial, sponsored by AstraZeneca and the NCI, that is being conducted in the United States and internationally. It is testing acalabrutinib with best supportive care versus BSC alone in people hospitalized with COVID-19. The trial is scheduled to be completed on Nov. 26.

Preliminary insights from this trial are expected soon. “These are not insights that we will likely publish, but they are important insights that will lead to the launch of a definitive double-blind, randomized, phase 3 trial, which we hope to launch in the next month or so,” Dr. Wilson said.
 

Targeting inflammation and infection simultaneously

Other scientists are investigating inhibitors of Janus kinase (JAK), a family of enzymes that play a key role in orchestrating immune responses, particularly cytokines. Interest in JAK inhibition to control hyperinflammation in cancer goes back at least 15 years, and drugs that act as JAK inhibitors are already approved for use in the treatment of myelofibrosis (ruxolitinib [Jakafi], fedratinib [Inrebic]) and also for rheumatoid arthritis (upadacitinib [Rinvoq], baricitinib [Olumiant]).

“It wasn’t a huge leap for those of us with a lot of understanding of JAK inhibitors to propose taking them into the clinic to treat patients with COVID-19,” commented John Mascarenhas, MD, the leader of clinical investigation in the myeloproliferative disorders program at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Mascarenhas is also principal investigator of the PRE-VENT trial, which is comparing the investigational JAK2 inhibitor pacritinib plus standard of care to standard of care alone in patients hospitalized with severe COVID-19, with and without cancer. The trial is sponsored by CTI BioPharma (manufacturer of pacritinib), and is taking place at 10 sites in the United States.

In a move that may raise eyebrows, PRE-VENT skipped phase 1 and 2 and went straight to phase 3. Pacritinib has yet to receive FDA approval and has mostly been studied in myelofibrosis, an intensely inflammatory disease.

The decision was based on trials of pacritinib in hematologic malignancies and also on results from a phase 2 study in China that found possible clinical benefit for the JAK 1/2 inhibitor ruxolitinib in 43 patients hospitalized with severe COVID-19, although results were not statistically significant, Dr. Mascarenhas explained.

Recent results from Lilly’s ACTT-2 study have provided further support for the role of JAK inhibitors in treating cytokine storm. ACTT-2 is a phase 3, double-blind, placebo-controlled, randomized, controlled trial sponsored by the NIH and NIAID comparing the JAK 1/2 inhibitor baricitinib plus the antiviral remdesivir with remdesivir alone in patients hospitalized with COVID-19. In September, Lilly announced that the trial met its primary endpoint of decreased time to recovery in patients who received baricitinib in combination with remdesivir.

But pacritinib’s mechanism of action may take things a step further. The drug selectively inhibits JAK2 and spares JAK1, which is important for antiviral activity in the immune system. Also, in vitro data suggests pacritinib may simultaneously reduce inflammation and fight off the virus by selectively inhibiting two additional enzymes and two other receptors.

“The rationale to me is very strong for using pacritinib,” Dr. Mascarenhas said. “I think this approach was bold but appropriate.”

The main safety concern with pacritinib could be bleeding, especially among patients on anticoagulants, Dr. Mascarenhas said. Because some patients with severe COVID-19 tend to develop blood clots, anticoagulation has become the standard of care at many institutions.

Because the trial is just beginning – only a minority of the total planned population of 358 patients has been enrolled – no interim results are available.
 

Right drug, wrong time?

IL-6 inhibition could still have a role to play in COVID-19, but the trick could be in the timing. Most of the trials so far have studied tocilizumab in patients with severe COVID-19, many of whom were already on ventilators. At that point, it may be too late to reverse the damage that has already taken place.

One of the main reasons tocilizumab works so well in CRS after CAR T therapy is that oncologists have learned how to use it early, often within 24 hours of fever onset. Oncologists use the American Society for Transplantation and Cellular Therapy consensus grading system, which helps them identify CRS when it is easier to control.

But applying the ASTCT grading system to COVID-19 is problematic. “Almost by definition, patients hospitalized with COVID-19 have low oxygen levels, which throws off the scale,” said Joshua Hill, MD, an infectious disease specialist at Fred Hutchinson Cancer Research Center in Seattle, who has research expertise in infectious complications after CAR T therapy.

“The key is to intervene earlier to prevent damage to the lungs and other end organs. We don’t have anything magical that will reverse that damage,” Dr. Hill said.

Results from the phase 3 trial EMPACTA trial (sponsored by Genentech) seem to bear this out. EMPACTA is evaluating use of tocilizumab in hospitalized patients with less severe COVID-19 who do not yet require mechanical ventilation. The trial is notable for being the first global phase 3 trial to demonstrate efficacy for tocilizumab vs placebo in hospitalized patients with COVID-19 pneumonia, and for including a high percentage of racial/ethnic minorities (85% of 389 participants), who have been hard hit by the pandemic and have historically been underrepresented in drug trials.

Last month, Roche announced that EMPACTA met its primary endpoint. Results showed that patients hospitalized with COVID-19 pneumonia who received tocilizumab plus standard of care were 44% less likely to go on mechanical ventilation or die, compared with those who received placebo plus standard of care (P = .0348), although there were no statistically significant differences in death by day 28 between tocilizumab and placebo (10.4% vs. 8.6%, P = .5146).

However, earlier administration of tocilizumab raises another issue. IL-6 and its pathway are important for clearing viral infections. Using tocilizumab in the context of an ongoing infection could raise safety issues.

Also, tocilizumab sticks around in the body for a relatively long time. In the treatment of rheumatoid arthritis, it is dosed once a month, and it carries a black box warning for reactivation of tuberculosis.

Whereas results from EMPACTA showed similar rates of infection associated with tocilizumab and placebo (10% vs. 11%), at least one other study has found increased rates of superinfection in patients with severe COVID-19 who received tocilizumab. Overall, though, the drug was associated with decreased risk of death in the latter study.

A phase 2 trial called COVIDOSE is tackling the safety issue. COVIDOSE is evaluating whether low-dose tocilizumab is effective in noncritical COVID-19 patients, with the idea that lower doses could be safer. Early results published as a preprint before peer review indicated that low-dose tocilizumab (ranging from 40 mg to 200 mg) was associated with clinical improvement in 32 noncritical patients hospitalized with COVID-19.

Five patients (15.6%) developed bacterial superinfections, and five (15.6%) died by 28-day follow-up, although there wasn’t a perfect “overlap” between these groups of patients. Bacterial superinfection was not the cause of death in all five patients who died, and not all patients who died developed bacterial superinfections, according to senior author Pankti Reid, MD, MPH, an assistant professor of medicine at the University of Chicago.

Results from COVIDOSE also showed that treatment with tocilizumab did not seem to affect the ability of patients to develop antibodies against COVID-19. The results set the stage for a larger randomized, controlled trial (still ongoing) to determine the optimal dose of tocilizumab.

Still, Dr. Hill urges caution.

Many of these immunomodulators have been used only in the context of a clinical trial, or only for patients with terminal cancer and no other treatment options. In patients with cancer, these drugs have been studied and have shown an “acceptable safety profile,” according to Dr. Shah.

But this is a different situation, and when it comes to repurposing them to relatively healthy patients with COVID-19, Dr. Hill emphasized the need for careful research.

“We’re always very concerned about giving drugs that suppress the immune response if people have active infections,” Dr. Hill said. “Often times we think it makes things worse, and it typically does.”

Dr. Mascarenhas reported institutional research funding from CTI Biopharma. Dr. Hill, Dr. Staudt, Dr. Wilson, and Dr. Shah disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

When the first reports emerged of “cytokine storm” in patients with severe COVID-19, all eyes turned to cancer research. Oncologists have years of experience reigning in “cytokine release syndrome” (CRS) in patients treated with chimeric antigen receptor (CAR) therapies for advanced blood cancers.

There was hope that drugs used to quell CRS in patients with cancer would be effective in patients with severe COVID. But the promise of a quick fix with oncology medications has yet to be fully realized.

Part of the problem is that the two conditions, while analogous, are “not the same,” said Nirali Shah, MD, head of the hematologic malignancies section in the pediatric oncology branch at the National Cancer Institute.

“You have to understand the underlying pathophysiology, what triggers the inflammation,” Dr. Shah said.

CAR T–related CRS is caused by activated T cells in patients with cancer who often do not have an infection, she explained. In contrast, cytokine storm in COVID-19 is triggered by a viral pathogen that can drive “out of control” inflammation. These differences may explain why drugs work in the first instance, but not in the second, she added. Drugs that inhibit interleukin-6 (such as tocilizumab, sarilumab, and siltuximab) are used with great success to dampen down the CRS in patients receiving CAR therapy for blood cancers. And although trials of these agents in patients with COVID are still ongoing, initial results are disappointing.

The first global, phase 3 randomized controlled trial of tocilizumab in severe COVID-19 failed to meet its primary endpoint of improved clinical status, and it did not meet its secondary endpoint of improved mortality at week 4.

In its recent recommendations, the National Institutes of Health noted a lack of data to support the efficacy of IL-6 inhibitors in COVID-19, and recommended against their use, except as part of a clinical trial.
 

Trimming the tree vs. cutting it down

As researchers have begun to decode the immune process underlying severe COVID-19, they have turned to other cancer drugs to tame cytokine storm.

Louis Staudt, MD, PhD, and Wyndham Wilson, MD, PhD, both at the NCI, think that cytokine storm in COVID-19 is driven by macrophages, which trigger release of multiple cytokines.

For years, the pair have been studying lymphoid tumors. Dr. Staudt is chief of the lymphoid malignancies branch at the NCI, and Wilson is head of the lymphoma therapeutics section. In past work, Dr. Staudt discovered that inhibiting an enzyme called bruton tyrosine kinase (BTK) dampens macrophage function.

When the pandemic began, Dr. Staudt and Dr. Wilson realized that singling out just one cytokine like IL-6 may not be enough. They thought that a more effective approach may be to target macrophages with a BTK inhibitor called acalabrutinib (Calquence), which would inhibit multiple cytokines at the same time.

Dr. Staudt likens the immune response to a tree, with the macrophages composing the tree trunk and the limbs made up of individual cytokines.

“Targeting macrophages is getting at the trunk of the problem,” he said. “You’re only cutting off the limbs with tocilizumab.”

In just 3 days, Dr. Staudt and Dr. Wilson went from concept to approval to launching a prospective, observational study. The study took place at five centers in the US, and included 19 patients hospitalized with COVID-19; the results were published in Science Immunology. Over a treatment course of 14 days, the majority of patients treated off-label with acalabrutinib improved, some within 24 hours. Eight of 11 patients on supplemental oxygen were discharged on room air. Four of eight patients on ventilators were extubated, with two of these discharged on room air. Two patients on ventilators died. No discernible toxicity was noted.

Analyses also showed increased BTK activity and elevated IL-6 levels in monocytes – precursors of macrophages – in patients with severe COVID-19, compared with healthy volunteers.

“We showed that the target of acalabrutinib was active in the immune cells of patients with severe COVID-19,” Dr. Staudt said. “So we have the target. We have the drug to hit the target. And we have an apparent clinical benefit.”

Those three things were compelling enough to launch the CALAVI phase 2 trial, an open-label, randomized, controlled trial, sponsored by AstraZeneca and the NCI, that is being conducted in the United States and internationally. It is testing acalabrutinib with best supportive care versus BSC alone in people hospitalized with COVID-19. The trial is scheduled to be completed on Nov. 26.

Preliminary insights from this trial are expected soon. “These are not insights that we will likely publish, but they are important insights that will lead to the launch of a definitive double-blind, randomized, phase 3 trial, which we hope to launch in the next month or so,” Dr. Wilson said.
 

Targeting inflammation and infection simultaneously

Other scientists are investigating inhibitors of Janus kinase (JAK), a family of enzymes that play a key role in orchestrating immune responses, particularly cytokines. Interest in JAK inhibition to control hyperinflammation in cancer goes back at least 15 years, and drugs that act as JAK inhibitors are already approved for use in the treatment of myelofibrosis (ruxolitinib [Jakafi], fedratinib [Inrebic]) and also for rheumatoid arthritis (upadacitinib [Rinvoq], baricitinib [Olumiant]).

“It wasn’t a huge leap for those of us with a lot of understanding of JAK inhibitors to propose taking them into the clinic to treat patients with COVID-19,” commented John Mascarenhas, MD, the leader of clinical investigation in the myeloproliferative disorders program at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Mascarenhas is also principal investigator of the PRE-VENT trial, which is comparing the investigational JAK2 inhibitor pacritinib plus standard of care to standard of care alone in patients hospitalized with severe COVID-19, with and without cancer. The trial is sponsored by CTI BioPharma (manufacturer of pacritinib), and is taking place at 10 sites in the United States.

In a move that may raise eyebrows, PRE-VENT skipped phase 1 and 2 and went straight to phase 3. Pacritinib has yet to receive FDA approval and has mostly been studied in myelofibrosis, an intensely inflammatory disease.

The decision was based on trials of pacritinib in hematologic malignancies and also on results from a phase 2 study in China that found possible clinical benefit for the JAK 1/2 inhibitor ruxolitinib in 43 patients hospitalized with severe COVID-19, although results were not statistically significant, Dr. Mascarenhas explained.

Recent results from Lilly’s ACTT-2 study have provided further support for the role of JAK inhibitors in treating cytokine storm. ACTT-2 is a phase 3, double-blind, placebo-controlled, randomized, controlled trial sponsored by the NIH and NIAID comparing the JAK 1/2 inhibitor baricitinib plus the antiviral remdesivir with remdesivir alone in patients hospitalized with COVID-19. In September, Lilly announced that the trial met its primary endpoint of decreased time to recovery in patients who received baricitinib in combination with remdesivir.

But pacritinib’s mechanism of action may take things a step further. The drug selectively inhibits JAK2 and spares JAK1, which is important for antiviral activity in the immune system. Also, in vitro data suggests pacritinib may simultaneously reduce inflammation and fight off the virus by selectively inhibiting two additional enzymes and two other receptors.

“The rationale to me is very strong for using pacritinib,” Dr. Mascarenhas said. “I think this approach was bold but appropriate.”

The main safety concern with pacritinib could be bleeding, especially among patients on anticoagulants, Dr. Mascarenhas said. Because some patients with severe COVID-19 tend to develop blood clots, anticoagulation has become the standard of care at many institutions.

Because the trial is just beginning – only a minority of the total planned population of 358 patients has been enrolled – no interim results are available.
 

Right drug, wrong time?

IL-6 inhibition could still have a role to play in COVID-19, but the trick could be in the timing. Most of the trials so far have studied tocilizumab in patients with severe COVID-19, many of whom were already on ventilators. At that point, it may be too late to reverse the damage that has already taken place.

One of the main reasons tocilizumab works so well in CRS after CAR T therapy is that oncologists have learned how to use it early, often within 24 hours of fever onset. Oncologists use the American Society for Transplantation and Cellular Therapy consensus grading system, which helps them identify CRS when it is easier to control.

But applying the ASTCT grading system to COVID-19 is problematic. “Almost by definition, patients hospitalized with COVID-19 have low oxygen levels, which throws off the scale,” said Joshua Hill, MD, an infectious disease specialist at Fred Hutchinson Cancer Research Center in Seattle, who has research expertise in infectious complications after CAR T therapy.

“The key is to intervene earlier to prevent damage to the lungs and other end organs. We don’t have anything magical that will reverse that damage,” Dr. Hill said.

Results from the phase 3 trial EMPACTA trial (sponsored by Genentech) seem to bear this out. EMPACTA is evaluating use of tocilizumab in hospitalized patients with less severe COVID-19 who do not yet require mechanical ventilation. The trial is notable for being the first global phase 3 trial to demonstrate efficacy for tocilizumab vs placebo in hospitalized patients with COVID-19 pneumonia, and for including a high percentage of racial/ethnic minorities (85% of 389 participants), who have been hard hit by the pandemic and have historically been underrepresented in drug trials.

Last month, Roche announced that EMPACTA met its primary endpoint. Results showed that patients hospitalized with COVID-19 pneumonia who received tocilizumab plus standard of care were 44% less likely to go on mechanical ventilation or die, compared with those who received placebo plus standard of care (P = .0348), although there were no statistically significant differences in death by day 28 between tocilizumab and placebo (10.4% vs. 8.6%, P = .5146).

However, earlier administration of tocilizumab raises another issue. IL-6 and its pathway are important for clearing viral infections. Using tocilizumab in the context of an ongoing infection could raise safety issues.

Also, tocilizumab sticks around in the body for a relatively long time. In the treatment of rheumatoid arthritis, it is dosed once a month, and it carries a black box warning for reactivation of tuberculosis.

Whereas results from EMPACTA showed similar rates of infection associated with tocilizumab and placebo (10% vs. 11%), at least one other study has found increased rates of superinfection in patients with severe COVID-19 who received tocilizumab. Overall, though, the drug was associated with decreased risk of death in the latter study.

A phase 2 trial called COVIDOSE is tackling the safety issue. COVIDOSE is evaluating whether low-dose tocilizumab is effective in noncritical COVID-19 patients, with the idea that lower doses could be safer. Early results published as a preprint before peer review indicated that low-dose tocilizumab (ranging from 40 mg to 200 mg) was associated with clinical improvement in 32 noncritical patients hospitalized with COVID-19.

Five patients (15.6%) developed bacterial superinfections, and five (15.6%) died by 28-day follow-up, although there wasn’t a perfect “overlap” between these groups of patients. Bacterial superinfection was not the cause of death in all five patients who died, and not all patients who died developed bacterial superinfections, according to senior author Pankti Reid, MD, MPH, an assistant professor of medicine at the University of Chicago.

Results from COVIDOSE also showed that treatment with tocilizumab did not seem to affect the ability of patients to develop antibodies against COVID-19. The results set the stage for a larger randomized, controlled trial (still ongoing) to determine the optimal dose of tocilizumab.

Still, Dr. Hill urges caution.

Many of these immunomodulators have been used only in the context of a clinical trial, or only for patients with terminal cancer and no other treatment options. In patients with cancer, these drugs have been studied and have shown an “acceptable safety profile,” according to Dr. Shah.

But this is a different situation, and when it comes to repurposing them to relatively healthy patients with COVID-19, Dr. Hill emphasized the need for careful research.

“We’re always very concerned about giving drugs that suppress the immune response if people have active infections,” Dr. Hill said. “Often times we think it makes things worse, and it typically does.”

Dr. Mascarenhas reported institutional research funding from CTI Biopharma. Dr. Hill, Dr. Staudt, Dr. Wilson, and Dr. Shah disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Delays in colorectal cancer screening due to the COVID-19 pandemic could lead to higher rates of advanced-stage cancer and death, according to a new study.

When compared with a delay of less than three months, the longer delay seen this year may result in an 11.9% increase in death rates.

“Across the globe, health care systems are facing serious difficulties while dealing with COVID-19, and it is imperative that support is given to the public and patients throughout the crisis, including for high-impact diseases such as colorectal cancer,” Luigi Ricciardiello, the lead study author and a professor at the University of Bologna in Italy, said in a statement.

Ricciardiello and colleagues presented their research on Monday at UEG Week Virtual 2020, an international conference for gastroenterologists. The study will be published in the UEG Journal .

The researchers created a model to forecast the effects of delayed cancer screening during 2020. A “moderate” delay of 7-12 months caused a 3% increase in advanced-stage colon cancer, and a long delay of more than 12 months caused a 7% increase in advanced cancer.

Based on a survival rate of 5 years for stage 3 or stage 4 colorectal cancer, the death rate would increase nearly 12% when screening is delayed for more than a year, as compared with less than three months of delay.

The research team found similar results when forecasting advanced-stage cancer and deaths earlier this year. In a paper published in Clinical Gastroenterology and Hepatology in early September, they projected that deaths could increase 12% if screening is delayed for more than a year.

Throughout the pandemic, screening programs have been delayed in many countries, particularly across Europe.

“Healthcare authorities need to act urgently on how they reorganise activities during COVID-19, without compromising the diagnosis of other high-impact diseases like this research shows,” Ricciardiello said.

United European Gastroenterology, a professional medical organization for digestive health specialists, has called for policymakers to implement colon cancer screening programs across the European Union. Annually, more than 375,000 new cases are diagnosed across the EU, and more than 170,000 people die from colorectal cancer, according to a UEG report.

“Early-stage diagnosis of colorectal cancer is crucial — it’s far easier to treat and enhances optimal patient outcomes,” Ricciardiello said. “It is therefore essential that vital diagnosis tools, like screening programmes, continue and help to prevent mortality rates from rising even further.”
 

This article first appeared on Medscape.com.

Delays in colorectal cancer screening due to the COVID-19 pandemic could lead to higher rates of advanced-stage cancer and death, according to a new study.

When compared with a delay of less than three months, the longer delay seen this year may result in an 11.9% increase in death rates.

“Across the globe, health care systems are facing serious difficulties while dealing with COVID-19, and it is imperative that support is given to the public and patients throughout the crisis, including for high-impact diseases such as colorectal cancer,” Luigi Ricciardiello, the lead study author and a professor at the University of Bologna in Italy, said in a statement.

Ricciardiello and colleagues presented their research on Monday at UEG Week Virtual 2020, an international conference for gastroenterologists. The study will be published in the UEG Journal .

The researchers created a model to forecast the effects of delayed cancer screening during 2020. A “moderate” delay of 7-12 months caused a 3% increase in advanced-stage colon cancer, and a long delay of more than 12 months caused a 7% increase in advanced cancer.

Based on a survival rate of 5 years for stage 3 or stage 4 colorectal cancer, the death rate would increase nearly 12% when screening is delayed for more than a year, as compared with less than three months of delay.

The research team found similar results when forecasting advanced-stage cancer and deaths earlier this year. In a paper published in Clinical Gastroenterology and Hepatology in early September, they projected that deaths could increase 12% if screening is delayed for more than a year.

Throughout the pandemic, screening programs have been delayed in many countries, particularly across Europe.

“Healthcare authorities need to act urgently on how they reorganise activities during COVID-19, without compromising the diagnosis of other high-impact diseases like this research shows,” Ricciardiello said.

United European Gastroenterology, a professional medical organization for digestive health specialists, has called for policymakers to implement colon cancer screening programs across the European Union. Annually, more than 375,000 new cases are diagnosed across the EU, and more than 170,000 people die from colorectal cancer, according to a UEG report.

“Early-stage diagnosis of colorectal cancer is crucial — it’s far easier to treat and enhances optimal patient outcomes,” Ricciardiello said. “It is therefore essential that vital diagnosis tools, like screening programmes, continue and help to prevent mortality rates from rising even further.”
 

This article first appeared on Medscape.com.

Delays in colorectal cancer screening due to the COVID-19 pandemic could lead to higher rates of advanced-stage cancer and death, according to a new study.

When compared with a delay of less than three months, the longer delay seen this year may result in an 11.9% increase in death rates.

“Across the globe, health care systems are facing serious difficulties while dealing with COVID-19, and it is imperative that support is given to the public and patients throughout the crisis, including for high-impact diseases such as colorectal cancer,” Luigi Ricciardiello, the lead study author and a professor at the University of Bologna in Italy, said in a statement.

Ricciardiello and colleagues presented their research on Monday at UEG Week Virtual 2020, an international conference for gastroenterologists. The study will be published in the UEG Journal .

The researchers created a model to forecast the effects of delayed cancer screening during 2020. A “moderate” delay of 7-12 months caused a 3% increase in advanced-stage colon cancer, and a long delay of more than 12 months caused a 7% increase in advanced cancer.

Based on a survival rate of 5 years for stage 3 or stage 4 colorectal cancer, the death rate would increase nearly 12% when screening is delayed for more than a year, as compared with less than three months of delay.

The research team found similar results when forecasting advanced-stage cancer and deaths earlier this year. In a paper published in Clinical Gastroenterology and Hepatology in early September, they projected that deaths could increase 12% if screening is delayed for more than a year.

Throughout the pandemic, screening programs have been delayed in many countries, particularly across Europe.

“Healthcare authorities need to act urgently on how they reorganise activities during COVID-19, without compromising the diagnosis of other high-impact diseases like this research shows,” Ricciardiello said.

United European Gastroenterology, a professional medical organization for digestive health specialists, has called for policymakers to implement colon cancer screening programs across the European Union. Annually, more than 375,000 new cases are diagnosed across the EU, and more than 170,000 people die from colorectal cancer, according to a UEG report.

“Early-stage diagnosis of colorectal cancer is crucial — it’s far easier to treat and enhances optimal patient outcomes,” Ricciardiello said. “It is therefore essential that vital diagnosis tools, like screening programmes, continue and help to prevent mortality rates from rising even further.”
 

This article first appeared on Medscape.com.