Key clinical point: Risankizumab effectively reduced clinical manifestations of psoriatic arthritis (PsA) in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with no new adverse events (AE).

Major finding: At week 24, at least a 20% improvement in the American College of Rheumatology score was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent AEs were mild/moderate and reported at similar frequencies in risankizumab (40.4%) and placebo (38.7%) groups.

Study details: Findings are from a double-blind, phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to ≥1 csDMARDs who were randomly assigned to receive 150 mg risankizumab or placebo at weeks 0, 4, and 16.

Disclosures: This study did not report any source of funding. The authors declared serving as speaker, consultant, investigator, or receiving honoraria, fees, and grants from several sources. Five authors declared being employees or shareholders of AbbVie.

Source: Kristensen LE et al. Ann Rheum Dis. 2021;81:225-231 (Dec 15). Doi: 10.1136/annrheumdis-2021-221019.

Key clinical point: Risankizumab effectively reduced clinical manifestations of psoriatic arthritis (PsA) in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with no new adverse events (AE).

Major finding: At week 24, at least a 20% improvement in the American College of Rheumatology score was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent AEs were mild/moderate and reported at similar frequencies in risankizumab (40.4%) and placebo (38.7%) groups.

Study details: Findings are from a double-blind, phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to ≥1 csDMARDs who were randomly assigned to receive 150 mg risankizumab or placebo at weeks 0, 4, and 16.

Disclosures: This study did not report any source of funding. The authors declared serving as speaker, consultant, investigator, or receiving honoraria, fees, and grants from several sources. Five authors declared being employees or shareholders of AbbVie.

Source: Kristensen LE et al. Ann Rheum Dis. 2021;81:225-231 (Dec 15). Doi: 10.1136/annrheumdis-2021-221019.

Key clinical point: Risankizumab effectively reduced clinical manifestations of psoriatic arthritis (PsA) in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with no new adverse events (AE).

Major finding: At week 24, at least a 20% improvement in the American College of Rheumatology score was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent AEs were mild/moderate and reported at similar frequencies in risankizumab (40.4%) and placebo (38.7%) groups.

Study details: Findings are from a double-blind, phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to ≥1 csDMARDs who were randomly assigned to receive 150 mg risankizumab or placebo at weeks 0, 4, and 16.

Disclosures: This study did not report any source of funding. The authors declared serving as speaker, consultant, investigator, or receiving honoraria, fees, and grants from several sources. Five authors declared being employees or shareholders of AbbVie.

Source: Kristensen LE et al. Ann Rheum Dis. 2021;81:225-231 (Dec 15). Doi: 10.1136/annrheumdis-2021-221019.

Key clinical point: In patients with psoriatic arthritis (PsA), clinical inflammation monitored by swollen joint counts (SJC) and biochemical inflammation monitored by C-reactive protein (CRP) level, have a direct effect on structural progression.

Major finding: Progression was significantly higher in patients with active vs. inactive time-averaged SJC (odds ratio [OR] 1.24; P = .016) and time-averaged CRP (OR 6.08; P = .036). Progression was greatest in presence of both clinical and biochemical inflammation and lowest in absence of both (P = .05).

Study details: Findings are secondary analysis of patient data from the IMPACT 2 trial, including 145 patients with PsA.

Disclosures: The study did not report any source of funding. The authors declared serving as associate editor or receiving grants and honoraria from several sources.

Source: Borst C et al. RMD Open. 2021;7:e002038 (Dec 8). Doi: 10.1136/rmdopen-2021-002038.

Key clinical point: In patients with psoriatic arthritis (PsA), clinical inflammation monitored by swollen joint counts (SJC) and biochemical inflammation monitored by C-reactive protein (CRP) level, have a direct effect on structural progression.

Major finding: Progression was significantly higher in patients with active vs. inactive time-averaged SJC (odds ratio [OR] 1.24; P = .016) and time-averaged CRP (OR 6.08; P = .036). Progression was greatest in presence of both clinical and biochemical inflammation and lowest in absence of both (P = .05).

Study details: Findings are secondary analysis of patient data from the IMPACT 2 trial, including 145 patients with PsA.

Disclosures: The study did not report any source of funding. The authors declared serving as associate editor or receiving grants and honoraria from several sources.

Source: Borst C et al. RMD Open. 2021;7:e002038 (Dec 8). Doi: 10.1136/rmdopen-2021-002038.

Key clinical point: In patients with psoriatic arthritis (PsA), clinical inflammation monitored by swollen joint counts (SJC) and biochemical inflammation monitored by C-reactive protein (CRP) level, have a direct effect on structural progression.

Major finding: Progression was significantly higher in patients with active vs. inactive time-averaged SJC (odds ratio [OR] 1.24; P = .016) and time-averaged CRP (OR 6.08; P = .036). Progression was greatest in presence of both clinical and biochemical inflammation and lowest in absence of both (P = .05).

Study details: Findings are secondary analysis of patient data from the IMPACT 2 trial, including 145 patients with PsA.

Disclosures: The study did not report any source of funding. The authors declared serving as associate editor or receiving grants and honoraria from several sources.

Source: Borst C et al. RMD Open. 2021;7:e002038 (Dec 8). Doi: 10.1136/rmdopen-2021-002038.

Key clinical point: Upadacitinib showed similar efficacy and a consistent safety profile as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) in patients with psoriatic arthritis (PsA).

Major finding: At week 12, ≥20% improvement in the American College of Rheumatology score was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI, 24.4%-43.1%; 30 mg: 45.7%; 95% CI, 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI, 27.9%-40.1%; 30 mg: 39.6%; 95% CI, 33.7%-45.5%). Adverse events were generally similar with monotherapy and combination therapy.

Study details: This is a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, including 1,916 patients with active PsA with an inadequate response to ≥1 nbDMARD/bDMARD who were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks.

Disclosures: This work was supported by AbbVie. Six authors reported being employees and stockholders of AbbVie. The other authors reported ties with several sources including AbbVie.

Source: Nash P et al. Rheumatology (Oxford). 2021;keab905 (Dec 3). Doi:  10.1093/rheumatology/keab905.

Key clinical point: Upadacitinib showed similar efficacy and a consistent safety profile as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) in patients with psoriatic arthritis (PsA).

Major finding: At week 12, ≥20% improvement in the American College of Rheumatology score was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI, 24.4%-43.1%; 30 mg: 45.7%; 95% CI, 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI, 27.9%-40.1%; 30 mg: 39.6%; 95% CI, 33.7%-45.5%). Adverse events were generally similar with monotherapy and combination therapy.

Study details: This is a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, including 1,916 patients with active PsA with an inadequate response to ≥1 nbDMARD/bDMARD who were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks.

Disclosures: This work was supported by AbbVie. Six authors reported being employees and stockholders of AbbVie. The other authors reported ties with several sources including AbbVie.

Source: Nash P et al. Rheumatology (Oxford). 2021;keab905 (Dec 3). Doi:  10.1093/rheumatology/keab905.

Key clinical point: Upadacitinib showed similar efficacy and a consistent safety profile as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) in patients with psoriatic arthritis (PsA).

Major finding: At week 12, ≥20% improvement in the American College of Rheumatology score was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI, 24.4%-43.1%; 30 mg: 45.7%; 95% CI, 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI, 27.9%-40.1%; 30 mg: 39.6%; 95% CI, 33.7%-45.5%). Adverse events were generally similar with monotherapy and combination therapy.

Study details: This is a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, including 1,916 patients with active PsA with an inadequate response to ≥1 nbDMARD/bDMARD who were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks.

Disclosures: This work was supported by AbbVie. Six authors reported being employees and stockholders of AbbVie. The other authors reported ties with several sources including AbbVie.

Source: Nash P et al. Rheumatology (Oxford). 2021;keab905 (Dec 3). Doi:  10.1093/rheumatology/keab905.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

Men and White people receive better treatment for gastroesophageal cancer than women, Blacks, and Latinos despite years of studies highlighting disparities in care, researchers say.

The problem is complex because it stems from both biological and socioeconomic factors, but some signs of improvement are beginning to show, said Nathaniel R. Evans III, MD, a professor of surgery at Thomas Jefferson University in Philadelphia.

“Repeatedly, we see that, although we know how patients should be treated, there are oftentimes subsets of patients who don’t receive that same level of care,” said Dr. Evans in a general session talk at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

Black patients with esophageal cancer are 38% more likely to die from the condition than White patients, he said, citing a 2013 study (Ann Surg Oncol. 2013 doi: 10.1245/s10434-012-2807-3). For Latino patients, mortality is 20% higher than for White patients.

The difference can mostly be explained by the rate of esophagectomy, which is 52% lower for Black patients and 29% lower for Latino patients, compared with White patients, the study found.

Besides race and gender, insurance status also influences who gets surgery, Dr. Evans said, citing data from the National Cancer Database. Black patients are less likely to get surgery and more likely to die at all stages and histologies, he said. They wait longer for treatment and are more likely to receive no treatment at all.

Women also suffer from disparities, said Anna Dorothea Wagner, MD, head of the gastrointestinal cancer clinic at Lausanne University Hospital in Lausanne (Switzerland), who spoke at the symposium with Dr Evans.

Seventy-five percent of men with esophageal and gastric adenocarcinoma get curative treatments, compared with only 60% of women, Dr. Wagner said, citing a 2020 study on which she is an author. Women are more likely to get palliative care. As a result, only 30% of women survive the condition for 5 years or more compared to 34% of men, she said. “At the moment we don’t know whether this is due to either patient preferences or cognitive or bias of physicians.”

Disparities in treatment outcomes because of biological differences

For women, some disparities also arise out of clear biological differences, Dr. Wagner said. Sex hormone signaling affects cancer susceptibility, and sex-biased gene expression signatures have been detected in multiple cancer types.

Women with poorly differentiated and signet-cell pathology are less likely to survive their cancer than men with the same histology, she said.

Many studies have shown that chemotherapy is more toxic to women than men without being more efficacious, she added. This suggests that the optimal doses might be different for women and men.

Responding to a question from the audience, Dr. Wagner said more research is needed on transgender patients to understand how these factors affect them.

Dr. Evans attributed the racial and ethnic disparities to some combination of differential histology, stage at diagnosis, access to care, socioeconomics, and inherent bias.

“The problem is not new,” Dr. Evans said. He described studies that found disparities in the 1970s. “But the good news is that things do seem to be getting better.”

Between 2000 and 2011, the number of esophagectomies being performed at high-volume hospitals increased, he said. The overall mortality after esophagectomy has consequently decreased over this time, and the gap in this rate between White and Black people has closed, he said. “Specialization and centralization clearly improve outcomes for certain surgical procedures.”

To address the problem everyone should acknowledge the disparities, particularly in the access to surgery. “I think one of the best tools we have to try to address the disparity is education, both for patients and providers,” Dr. Evans said.

Care teams must become more diverse and culturally competent to combat longstanding distrust and improve communication, he said.

In December, ASCO announced an “action plan” to address equity, diversity and inclusion in cancer care. The organization promised to improve clinical trial eligibility, and train researchers about inherent bias in order to make the trials more representative of the cancer population.

It vowed to increase participation of underrepresented groups in its professional development programs and leadership roles, and educate its members about equity. And, it resolved to provide resources to providers so they could advocate for better quality of care, especially in rural and disadvantaged settings.

Dr. Wagner disclosed relationships with Alligator Bioscience, BMS, Dragonfly Therapeutics, Lilly, Merck KGaA, MSD Oncology, Servier/Pfizer, and Abbvie. Dr. Evans disclosed relationships with Bristol Myers Squibb Foundation and Intuitive Surgical.

This article was updated 1/28/22.

Men and White people receive better treatment for gastroesophageal cancer than women, Blacks, and Latinos despite years of studies highlighting disparities in care, researchers say.

The problem is complex because it stems from both biological and socioeconomic factors, but some signs of improvement are beginning to show, said Nathaniel R. Evans III, MD, a professor of surgery at Thomas Jefferson University in Philadelphia.

“Repeatedly, we see that, although we know how patients should be treated, there are oftentimes subsets of patients who don’t receive that same level of care,” said Dr. Evans in a general session talk at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

Black patients with esophageal cancer are 38% more likely to die from the condition than White patients, he said, citing a 2013 study (Ann Surg Oncol. 2013 doi: 10.1245/s10434-012-2807-3). For Latino patients, mortality is 20% higher than for White patients.

The difference can mostly be explained by the rate of esophagectomy, which is 52% lower for Black patients and 29% lower for Latino patients, compared with White patients, the study found.

Besides race and gender, insurance status also influences who gets surgery, Dr. Evans said, citing data from the National Cancer Database. Black patients are less likely to get surgery and more likely to die at all stages and histologies, he said. They wait longer for treatment and are more likely to receive no treatment at all.

Women also suffer from disparities, said Anna Dorothea Wagner, MD, head of the gastrointestinal cancer clinic at Lausanne University Hospital in Lausanne (Switzerland), who spoke at the symposium with Dr Evans.

Seventy-five percent of men with esophageal and gastric adenocarcinoma get curative treatments, compared with only 60% of women, Dr. Wagner said, citing a 2020 study on which she is an author. Women are more likely to get palliative care. As a result, only 30% of women survive the condition for 5 years or more compared to 34% of men, she said. “At the moment we don’t know whether this is due to either patient preferences or cognitive or bias of physicians.”

Disparities in treatment outcomes because of biological differences

For women, some disparities also arise out of clear biological differences, Dr. Wagner said. Sex hormone signaling affects cancer susceptibility, and sex-biased gene expression signatures have been detected in multiple cancer types.

Women with poorly differentiated and signet-cell pathology are less likely to survive their cancer than men with the same histology, she said.

Many studies have shown that chemotherapy is more toxic to women than men without being more efficacious, she added. This suggests that the optimal doses might be different for women and men.

Responding to a question from the audience, Dr. Wagner said more research is needed on transgender patients to understand how these factors affect them.

Dr. Evans attributed the racial and ethnic disparities to some combination of differential histology, stage at diagnosis, access to care, socioeconomics, and inherent bias.

“The problem is not new,” Dr. Evans said. He described studies that found disparities in the 1970s. “But the good news is that things do seem to be getting better.”

Between 2000 and 2011, the number of esophagectomies being performed at high-volume hospitals increased, he said. The overall mortality after esophagectomy has consequently decreased over this time, and the gap in this rate between White and Black people has closed, he said. “Specialization and centralization clearly improve outcomes for certain surgical procedures.”

To address the problem everyone should acknowledge the disparities, particularly in the access to surgery. “I think one of the best tools we have to try to address the disparity is education, both for patients and providers,” Dr. Evans said.

Care teams must become more diverse and culturally competent to combat longstanding distrust and improve communication, he said.

In December, ASCO announced an “action plan” to address equity, diversity and inclusion in cancer care. The organization promised to improve clinical trial eligibility, and train researchers about inherent bias in order to make the trials more representative of the cancer population.

It vowed to increase participation of underrepresented groups in its professional development programs and leadership roles, and educate its members about equity. And, it resolved to provide resources to providers so they could advocate for better quality of care, especially in rural and disadvantaged settings.

Dr. Wagner disclosed relationships with Alligator Bioscience, BMS, Dragonfly Therapeutics, Lilly, Merck KGaA, MSD Oncology, Servier/Pfizer, and Abbvie. Dr. Evans disclosed relationships with Bristol Myers Squibb Foundation and Intuitive Surgical.

This article was updated 1/28/22.

Men and White people receive better treatment for gastroesophageal cancer than women, Blacks, and Latinos despite years of studies highlighting disparities in care, researchers say.

The problem is complex because it stems from both biological and socioeconomic factors, but some signs of improvement are beginning to show, said Nathaniel R. Evans III, MD, a professor of surgery at Thomas Jefferson University in Philadelphia.

“Repeatedly, we see that, although we know how patients should be treated, there are oftentimes subsets of patients who don’t receive that same level of care,” said Dr. Evans in a general session talk at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

Black patients with esophageal cancer are 38% more likely to die from the condition than White patients, he said, citing a 2013 study (Ann Surg Oncol. 2013 doi: 10.1245/s10434-012-2807-3). For Latino patients, mortality is 20% higher than for White patients.

The difference can mostly be explained by the rate of esophagectomy, which is 52% lower for Black patients and 29% lower for Latino patients, compared with White patients, the study found.

Besides race and gender, insurance status also influences who gets surgery, Dr. Evans said, citing data from the National Cancer Database. Black patients are less likely to get surgery and more likely to die at all stages and histologies, he said. They wait longer for treatment and are more likely to receive no treatment at all.

Women also suffer from disparities, said Anna Dorothea Wagner, MD, head of the gastrointestinal cancer clinic at Lausanne University Hospital in Lausanne (Switzerland), who spoke at the symposium with Dr Evans.

Seventy-five percent of men with esophageal and gastric adenocarcinoma get curative treatments, compared with only 60% of women, Dr. Wagner said, citing a 2020 study on which she is an author. Women are more likely to get palliative care. As a result, only 30% of women survive the condition for 5 years or more compared to 34% of men, she said. “At the moment we don’t know whether this is due to either patient preferences or cognitive or bias of physicians.”

Disparities in treatment outcomes because of biological differences

For women, some disparities also arise out of clear biological differences, Dr. Wagner said. Sex hormone signaling affects cancer susceptibility, and sex-biased gene expression signatures have been detected in multiple cancer types.

Women with poorly differentiated and signet-cell pathology are less likely to survive their cancer than men with the same histology, she said.

Many studies have shown that chemotherapy is more toxic to women than men without being more efficacious, she added. This suggests that the optimal doses might be different for women and men.

Responding to a question from the audience, Dr. Wagner said more research is needed on transgender patients to understand how these factors affect them.

Dr. Evans attributed the racial and ethnic disparities to some combination of differential histology, stage at diagnosis, access to care, socioeconomics, and inherent bias.

“The problem is not new,” Dr. Evans said. He described studies that found disparities in the 1970s. “But the good news is that things do seem to be getting better.”

Between 2000 and 2011, the number of esophagectomies being performed at high-volume hospitals increased, he said. The overall mortality after esophagectomy has consequently decreased over this time, and the gap in this rate between White and Black people has closed, he said. “Specialization and centralization clearly improve outcomes for certain surgical procedures.”

To address the problem everyone should acknowledge the disparities, particularly in the access to surgery. “I think one of the best tools we have to try to address the disparity is education, both for patients and providers,” Dr. Evans said.

Care teams must become more diverse and culturally competent to combat longstanding distrust and improve communication, he said.

In December, ASCO announced an “action plan” to address equity, diversity and inclusion in cancer care. The organization promised to improve clinical trial eligibility, and train researchers about inherent bias in order to make the trials more representative of the cancer population.

It vowed to increase participation of underrepresented groups in its professional development programs and leadership roles, and educate its members about equity. And, it resolved to provide resources to providers so they could advocate for better quality of care, especially in rural and disadvantaged settings.

Dr. Wagner disclosed relationships with Alligator Bioscience, BMS, Dragonfly Therapeutics, Lilly, Merck KGaA, MSD Oncology, Servier/Pfizer, and Abbvie. Dr. Evans disclosed relationships with Bristol Myers Squibb Foundation and Intuitive Surgical.

This article was updated 1/28/22.

A new French study raises the possibility that immunotherapy can help some people with stomach cancer avoid surgery.

GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.

Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.

After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.

If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.

The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.

At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.

They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.

Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.

Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.

Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.

There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.

The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.

Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.

A new French study raises the possibility that immunotherapy can help some people with stomach cancer avoid surgery.

GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.

Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.

After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.

If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.

The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.

At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.

They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.

Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.

Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.

Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.

There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.

The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.

Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.

A new French study raises the possibility that immunotherapy can help some people with stomach cancer avoid surgery.

GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.

Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.

After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.

If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.

The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.

At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.

They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.

Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.

Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.

Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.

There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.

The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.

Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.

Allopurinol treatment is not associated with increased mortality in patients with gout and chronic kidney disease even at 5 years after starting treatment, a study has found.

Around one in five patients with gout also have chronic kidney disease, and previous research suggests that hyperuricemia is itself a contributor to renal disease, which is why there has been interest in the use of serum urate–lowering medication in patients with both conditions.

Since the publication of two earlier randomized controlled trials suggested a twofold increase in mortality among patients with renal disease who were treated with allopurinol in an attempt to slow progression, there has been wariness about the drug in patients with compromised renal function.

©joloei/Thinkstock

In a study published in Annals of Internal Medicine, Jie Wei, PhD, of Xiangya Hospital at Central South University in Changsha, China, and coauthors report the results of their retrospective, population-based study of 5,277 adults aged 40 and older with gout and moderate to severe chronic kidney disease who were initiated on allopurinol and 5,277 matched individuals not on allopurinol.

At 5 years after the patients started allopurinol, the study found that mortality was a statistically significant 15% lower (hazard ratio, 0.85; 95% confidence interval, 0.77-0.93) among those on allopurinol, compared with those not taking the drug. The rate was 4.9 deaths per 100 person-years among those on allopurinol, compared with 5.8 among those not taking it.

The researchers also created two simulated randomized clinical trials from the data for initiators of allopurinol, replicating each initiator twice. The first trial assigned patient replicates either to achieving a target serum urate level of less than 0.36 mmol/L within a year or not achieving it. The second assigned patient replicates to either an allopurinol dose-escalation group or no dose escalation.

For the target serum urate level study, 1,484 achieved the target, and this was associated with a 13% lower hazard ratio for mortality that just missed statistical significance (HR, 0.87; 95% confidence interval, 0.75-1.01).

In the dose-escalation study, there were 773 participants who increased their dose of allopurinol in the first year after initiation – from a median of 100 mg/day to a median final dose of 300 mg/day – and 2,923 who didn’t. Those who escalated their dose had a nonsignificant 12% lower risk of mortality (HR, 0.88; 95% CI, 0.73-1.07), compared with those who didn’t.

The authors suggest that this could be the result of confounding, as patients who achieved target serum urate levels may have been of better health generally than those who didn’t, which could also have contributed to lower mortality.

Coauthor of the study Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, Boston, said there had previously been a theory that allopurinol could protect against progression of renal disease. However, the two randomized, controlled trials in patients with chronic kidney disease but not gout published in 2020 suggested that allopurinol was instead associated with a doubling of mortality in this group.

“This study really shows convincing evidence that among gout patients with renal disease, allopurinol does not increase mortality,” Dr. Zhang told this news organization. He suggested the reason that the earlier studies had found higher mortality among patients on allopurinol was because those patients did not have gout. Given that gout can increase mortality, treating it effectively with allopurinol may therefore reduce mortality even in patients with concurrent chronic kidney disease.

Commenting on the study, Angelo Gaffo, MD, from the Birmingham VA Medical Center and the division of rheumatology at the University of Alabama at Birmingham, said that, while there had been data suggesting increased mortality, the findings from this “very well-done” study were reassuring and even suggested a possible decrease in mortality associated with allopurinol.

“I wouldn’t scream it out loud because it needs confirmation, but it’s something also that we have a sense that could be true,” he said.

Dr. Gaffo noted that patients treated with allopurinol tended to be those with fewer comorbidities. “Patients who have a lot of comorbidities probably are less likely to have their dose of allopurinol started or increased because of some concerns that practitioners may have about putting them on another medicine or increasing the dose of that medicine,” he said.

He also stressed that the findings still need replication in other large database studies, given that a prospective, randomized clinical trial addressing such a question would be difficult to conduct.

The study was supported by the Project Program of National Clinical Research Center for Geriatric Disorders, the National Natural Science Foundation of China, and the U.S. National Institutes of Health. Two authors reported consulting fees from the pharmaceutical sector unrelated to the study. No other conflicts of interest were declared.

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

Allopurinol treatment is not associated with increased mortality in patients with gout and chronic kidney disease even at 5 years after starting treatment, a study has found.

Around one in five patients with gout also have chronic kidney disease, and previous research suggests that hyperuricemia is itself a contributor to renal disease, which is why there has been interest in the use of serum urate–lowering medication in patients with both conditions.

Since the publication of two earlier randomized controlled trials suggested a twofold increase in mortality among patients with renal disease who were treated with allopurinol in an attempt to slow progression, there has been wariness about the drug in patients with compromised renal function.

©joloei/Thinkstock

In a study published in Annals of Internal Medicine, Jie Wei, PhD, of Xiangya Hospital at Central South University in Changsha, China, and coauthors report the results of their retrospective, population-based study of 5,277 adults aged 40 and older with gout and moderate to severe chronic kidney disease who were initiated on allopurinol and 5,277 matched individuals not on allopurinol.

At 5 years after the patients started allopurinol, the study found that mortality was a statistically significant 15% lower (hazard ratio, 0.85; 95% confidence interval, 0.77-0.93) among those on allopurinol, compared with those not taking the drug. The rate was 4.9 deaths per 100 person-years among those on allopurinol, compared with 5.8 among those not taking it.

The researchers also created two simulated randomized clinical trials from the data for initiators of allopurinol, replicating each initiator twice. The first trial assigned patient replicates either to achieving a target serum urate level of less than 0.36 mmol/L within a year or not achieving it. The second assigned patient replicates to either an allopurinol dose-escalation group or no dose escalation.

For the target serum urate level study, 1,484 achieved the target, and this was associated with a 13% lower hazard ratio for mortality that just missed statistical significance (HR, 0.87; 95% confidence interval, 0.75-1.01).

In the dose-escalation study, there were 773 participants who increased their dose of allopurinol in the first year after initiation – from a median of 100 mg/day to a median final dose of 300 mg/day – and 2,923 who didn’t. Those who escalated their dose had a nonsignificant 12% lower risk of mortality (HR, 0.88; 95% CI, 0.73-1.07), compared with those who didn’t.

The authors suggest that this could be the result of confounding, as patients who achieved target serum urate levels may have been of better health generally than those who didn’t, which could also have contributed to lower mortality.

Coauthor of the study Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, Boston, said there had previously been a theory that allopurinol could protect against progression of renal disease. However, the two randomized, controlled trials in patients with chronic kidney disease but not gout published in 2020 suggested that allopurinol was instead associated with a doubling of mortality in this group.

“This study really shows convincing evidence that among gout patients with renal disease, allopurinol does not increase mortality,” Dr. Zhang told this news organization. He suggested the reason that the earlier studies had found higher mortality among patients on allopurinol was because those patients did not have gout. Given that gout can increase mortality, treating it effectively with allopurinol may therefore reduce mortality even in patients with concurrent chronic kidney disease.

Commenting on the study, Angelo Gaffo, MD, from the Birmingham VA Medical Center and the division of rheumatology at the University of Alabama at Birmingham, said that, while there had been data suggesting increased mortality, the findings from this “very well-done” study were reassuring and even suggested a possible decrease in mortality associated with allopurinol.

“I wouldn’t scream it out loud because it needs confirmation, but it’s something also that we have a sense that could be true,” he said.

Dr. Gaffo noted that patients treated with allopurinol tended to be those with fewer comorbidities. “Patients who have a lot of comorbidities probably are less likely to have their dose of allopurinol started or increased because of some concerns that practitioners may have about putting them on another medicine or increasing the dose of that medicine,” he said.

He also stressed that the findings still need replication in other large database studies, given that a prospective, randomized clinical trial addressing such a question would be difficult to conduct.

The study was supported by the Project Program of National Clinical Research Center for Geriatric Disorders, the National Natural Science Foundation of China, and the U.S. National Institutes of Health. Two authors reported consulting fees from the pharmaceutical sector unrelated to the study. No other conflicts of interest were declared.

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

Allopurinol treatment is not associated with increased mortality in patients with gout and chronic kidney disease even at 5 years after starting treatment, a study has found.

Around one in five patients with gout also have chronic kidney disease, and previous research suggests that hyperuricemia is itself a contributor to renal disease, which is why there has been interest in the use of serum urate–lowering medication in patients with both conditions.

Since the publication of two earlier randomized controlled trials suggested a twofold increase in mortality among patients with renal disease who were treated with allopurinol in an attempt to slow progression, there has been wariness about the drug in patients with compromised renal function.

©joloei/Thinkstock

In a study published in Annals of Internal Medicine, Jie Wei, PhD, of Xiangya Hospital at Central South University in Changsha, China, and coauthors report the results of their retrospective, population-based study of 5,277 adults aged 40 and older with gout and moderate to severe chronic kidney disease who were initiated on allopurinol and 5,277 matched individuals not on allopurinol.

At 5 years after the patients started allopurinol, the study found that mortality was a statistically significant 15% lower (hazard ratio, 0.85; 95% confidence interval, 0.77-0.93) among those on allopurinol, compared with those not taking the drug. The rate was 4.9 deaths per 100 person-years among those on allopurinol, compared with 5.8 among those not taking it.

The researchers also created two simulated randomized clinical trials from the data for initiators of allopurinol, replicating each initiator twice. The first trial assigned patient replicates either to achieving a target serum urate level of less than 0.36 mmol/L within a year or not achieving it. The second assigned patient replicates to either an allopurinol dose-escalation group or no dose escalation.

For the target serum urate level study, 1,484 achieved the target, and this was associated with a 13% lower hazard ratio for mortality that just missed statistical significance (HR, 0.87; 95% confidence interval, 0.75-1.01).

In the dose-escalation study, there were 773 participants who increased their dose of allopurinol in the first year after initiation – from a median of 100 mg/day to a median final dose of 300 mg/day – and 2,923 who didn’t. Those who escalated their dose had a nonsignificant 12% lower risk of mortality (HR, 0.88; 95% CI, 0.73-1.07), compared with those who didn’t.

The authors suggest that this could be the result of confounding, as patients who achieved target serum urate levels may have been of better health generally than those who didn’t, which could also have contributed to lower mortality.

Coauthor of the study Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, Boston, said there had previously been a theory that allopurinol could protect against progression of renal disease. However, the two randomized, controlled trials in patients with chronic kidney disease but not gout published in 2020 suggested that allopurinol was instead associated with a doubling of mortality in this group.

“This study really shows convincing evidence that among gout patients with renal disease, allopurinol does not increase mortality,” Dr. Zhang told this news organization. He suggested the reason that the earlier studies had found higher mortality among patients on allopurinol was because those patients did not have gout. Given that gout can increase mortality, treating it effectively with allopurinol may therefore reduce mortality even in patients with concurrent chronic kidney disease.

Commenting on the study, Angelo Gaffo, MD, from the Birmingham VA Medical Center and the division of rheumatology at the University of Alabama at Birmingham, said that, while there had been data suggesting increased mortality, the findings from this “very well-done” study were reassuring and even suggested a possible decrease in mortality associated with allopurinol.

“I wouldn’t scream it out loud because it needs confirmation, but it’s something also that we have a sense that could be true,” he said.

Dr. Gaffo noted that patients treated with allopurinol tended to be those with fewer comorbidities. “Patients who have a lot of comorbidities probably are less likely to have their dose of allopurinol started or increased because of some concerns that practitioners may have about putting them on another medicine or increasing the dose of that medicine,” he said.

He also stressed that the findings still need replication in other large database studies, given that a prospective, randomized clinical trial addressing such a question would be difficult to conduct.

The study was supported by the Project Program of National Clinical Research Center for Geriatric Disorders, the National Natural Science Foundation of China, and the U.S. National Institutes of Health. Two authors reported consulting fees from the pharmaceutical sector unrelated to the study. No other conflicts of interest were declared.

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

Although the risk of developing lymphoma in association with a breast implant is “considered to be low,” the disease is “serious and can lead to death,” according to the U.S. Food and Drug Administration.

The immediate treatment is surgical removal of the implant, which is sometimes followed with chemotherapy.

New data show that women who develop breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) who require chemotherapy can achieve excellent results with a combination of chemotherapy (cyclophosphamide, doxorubicin, and prednisone) and the antibody–drug conjugate brentuximab vedotin.

The findings were published in Blood.

The authors, led by Fabien Le Bras, MD, from the Henri Mondor Hospital, Créteil, France, note that despite BIA-ALCL being recently recognized as a provisional entity by the World Health Organization, its pathogenesis has yet to be fully elucidated, and a standard of care has not been established.

Results from the ECHELON 2 trial established brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) as a new standard of care in CD30-positive peripheral T-cell lymphoma.

That trial included 316 patients with ACLC, although none of these cases were associated with breast implants.

The principal investigator on that trial, Steven Horwitz, MD, from Memorial Sloan Kettering Center, New York, told this news organization that although BIA-ALCL is “incredibly rare,” it causes “distress” to patients, as “many of them made a choice for reconstruction ... that they thought was safe.”

He said that the latest data from France is “interesting” and that the application of the ECHELON-2 findings to BIA-ALCL is “very logical.”

“For the people who need systemic therapy,” it appears from the current results that BV-CHP “is a very good option,” he said.

The “difficulty” in interpreting the data, however, is that “perhaps 80% of people with BIA-ALCL don’t need any systemic therapy” and are “cured with surgery alone.”

Dr. Horwitz said that while patients with infiltrative disease have a “higher risk of recurrence ... many of those are still cured with surgery alone.”

The main outstanding question he has is how many of the patients who received BV-CHP “might have been okay with observation.”
 

Details of the new data from France

For their study, Dr. Le Bras and colleagues analyzed data from the Lymphoma Study Association registry between 2009 and 2021 and identified 85 patients with BIA-ALCL, including 73 in France and 12 in Belgium.

Most of these patients (whose median age was 57 years) had unilateral lymphoma (94.1%), and only a few patients (5.9%) had bilateral disease.

The team notes that 41.2% of these women had received breast implants once, 41.2% received implants twice, and 17.6% received them three times or more.

In 45.9% of cases, the first implant followed mastectomy for breast cancer.

All patients had at least one textured implant. These have been associated with more cases of BIA-ALCL than smooth implants, and in 2019, Allergan recalled all BioCell textured breast implant products from the United States and around the world, due to the risk for BIA-ALCL, as reported, at the time, by this news organization.

For the women in this registry, the median time from the last implant to BIA-ALCL diagnosis was 7 years.

The most common presentation was seroma, which occurred in 75.3% of patients, while 21.2% of had a breast tumor mass with or without seroma.

Stage I-II disease was identified in 76.5% of patients, and 21.2% of cases were stage IV. Infiltrative disease was present in 24.7%.

Implant removal with total capsulectomy was performed in 77.6%; 29.4% of women also received chemotherapy, with 11.8% receiving BV-CHP.

A complete response was achieved in 84% of patients who received chemotherapy, while 8% failed to respond. Among the patients who received BV-CHP, 80% achieved a complete response.

After a median follow-up of 28.6 months, 91.8% patients were alive and progression free. All patients treated with BV-CHP were alive and progression free after a median follow-up of 1 year.

Patients with infiltrative disease had a significantly worse 2-year progression-free survival than those with in situ/mixed disease, at 73.8% versus 96.7%, or a hazard ratio for progression of 5.3 (P = .0039).

They also had worse 2-year overall survival, at 78.7% versus 100%, or a hazard ratio for death of 8.5 (P = .0022).

The authors note that these patients with infiltrative disease had significantly worse survival outcomes and may benefit most from BV-CHP.

No funding for the study was declared. Dr. Le Bras reports relationships with Novartis, Celgene, BMS, Takeda, Kite, and Gilead. Other authors declare numerous relevant financial relationships.

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

Although the risk of developing lymphoma in association with a breast implant is “considered to be low,” the disease is “serious and can lead to death,” according to the U.S. Food and Drug Administration.

The immediate treatment is surgical removal of the implant, which is sometimes followed with chemotherapy.

New data show that women who develop breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) who require chemotherapy can achieve excellent results with a combination of chemotherapy (cyclophosphamide, doxorubicin, and prednisone) and the antibody–drug conjugate brentuximab vedotin.

The findings were published in Blood.

The authors, led by Fabien Le Bras, MD, from the Henri Mondor Hospital, Créteil, France, note that despite BIA-ALCL being recently recognized as a provisional entity by the World Health Organization, its pathogenesis has yet to be fully elucidated, and a standard of care has not been established.

Results from the ECHELON 2 trial established brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) as a new standard of care in CD30-positive peripheral T-cell lymphoma.

That trial included 316 patients with ACLC, although none of these cases were associated with breast implants.

The principal investigator on that trial, Steven Horwitz, MD, from Memorial Sloan Kettering Center, New York, told this news organization that although BIA-ALCL is “incredibly rare,” it causes “distress” to patients, as “many of them made a choice for reconstruction ... that they thought was safe.”

He said that the latest data from France is “interesting” and that the application of the ECHELON-2 findings to BIA-ALCL is “very logical.”

“For the people who need systemic therapy,” it appears from the current results that BV-CHP “is a very good option,” he said.

The “difficulty” in interpreting the data, however, is that “perhaps 80% of people with BIA-ALCL don’t need any systemic therapy” and are “cured with surgery alone.”

Dr. Horwitz said that while patients with infiltrative disease have a “higher risk of recurrence ... many of those are still cured with surgery alone.”

The main outstanding question he has is how many of the patients who received BV-CHP “might have been okay with observation.”
 

Details of the new data from France

For their study, Dr. Le Bras and colleagues analyzed data from the Lymphoma Study Association registry between 2009 and 2021 and identified 85 patients with BIA-ALCL, including 73 in France and 12 in Belgium.

Most of these patients (whose median age was 57 years) had unilateral lymphoma (94.1%), and only a few patients (5.9%) had bilateral disease.

The team notes that 41.2% of these women had received breast implants once, 41.2% received implants twice, and 17.6% received them three times or more.

In 45.9% of cases, the first implant followed mastectomy for breast cancer.

All patients had at least one textured implant. These have been associated with more cases of BIA-ALCL than smooth implants, and in 2019, Allergan recalled all BioCell textured breast implant products from the United States and around the world, due to the risk for BIA-ALCL, as reported, at the time, by this news organization.

For the women in this registry, the median time from the last implant to BIA-ALCL diagnosis was 7 years.

The most common presentation was seroma, which occurred in 75.3% of patients, while 21.2% of had a breast tumor mass with or without seroma.

Stage I-II disease was identified in 76.5% of patients, and 21.2% of cases were stage IV. Infiltrative disease was present in 24.7%.

Implant removal with total capsulectomy was performed in 77.6%; 29.4% of women also received chemotherapy, with 11.8% receiving BV-CHP.

A complete response was achieved in 84% of patients who received chemotherapy, while 8% failed to respond. Among the patients who received BV-CHP, 80% achieved a complete response.

After a median follow-up of 28.6 months, 91.8% patients were alive and progression free. All patients treated with BV-CHP were alive and progression free after a median follow-up of 1 year.

Patients with infiltrative disease had a significantly worse 2-year progression-free survival than those with in situ/mixed disease, at 73.8% versus 96.7%, or a hazard ratio for progression of 5.3 (P = .0039).

They also had worse 2-year overall survival, at 78.7% versus 100%, or a hazard ratio for death of 8.5 (P = .0022).

The authors note that these patients with infiltrative disease had significantly worse survival outcomes and may benefit most from BV-CHP.

No funding for the study was declared. Dr. Le Bras reports relationships with Novartis, Celgene, BMS, Takeda, Kite, and Gilead. Other authors declare numerous relevant financial relationships.

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

Although the risk of developing lymphoma in association with a breast implant is “considered to be low,” the disease is “serious and can lead to death,” according to the U.S. Food and Drug Administration.

The immediate treatment is surgical removal of the implant, which is sometimes followed with chemotherapy.

New data show that women who develop breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) who require chemotherapy can achieve excellent results with a combination of chemotherapy (cyclophosphamide, doxorubicin, and prednisone) and the antibody–drug conjugate brentuximab vedotin.

The findings were published in Blood.

The authors, led by Fabien Le Bras, MD, from the Henri Mondor Hospital, Créteil, France, note that despite BIA-ALCL being recently recognized as a provisional entity by the World Health Organization, its pathogenesis has yet to be fully elucidated, and a standard of care has not been established.

Results from the ECHELON 2 trial established brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV-CHP) as a new standard of care in CD30-positive peripheral T-cell lymphoma.

That trial included 316 patients with ACLC, although none of these cases were associated with breast implants.

The principal investigator on that trial, Steven Horwitz, MD, from Memorial Sloan Kettering Center, New York, told this news organization that although BIA-ALCL is “incredibly rare,” it causes “distress” to patients, as “many of them made a choice for reconstruction ... that they thought was safe.”

He said that the latest data from France is “interesting” and that the application of the ECHELON-2 findings to BIA-ALCL is “very logical.”

“For the people who need systemic therapy,” it appears from the current results that BV-CHP “is a very good option,” he said.

The “difficulty” in interpreting the data, however, is that “perhaps 80% of people with BIA-ALCL don’t need any systemic therapy” and are “cured with surgery alone.”

Dr. Horwitz said that while patients with infiltrative disease have a “higher risk of recurrence ... many of those are still cured with surgery alone.”

The main outstanding question he has is how many of the patients who received BV-CHP “might have been okay with observation.”
 

Details of the new data from France

For their study, Dr. Le Bras and colleagues analyzed data from the Lymphoma Study Association registry between 2009 and 2021 and identified 85 patients with BIA-ALCL, including 73 in France and 12 in Belgium.

Most of these patients (whose median age was 57 years) had unilateral lymphoma (94.1%), and only a few patients (5.9%) had bilateral disease.

The team notes that 41.2% of these women had received breast implants once, 41.2% received implants twice, and 17.6% received them three times or more.

In 45.9% of cases, the first implant followed mastectomy for breast cancer.

All patients had at least one textured implant. These have been associated with more cases of BIA-ALCL than smooth implants, and in 2019, Allergan recalled all BioCell textured breast implant products from the United States and around the world, due to the risk for BIA-ALCL, as reported, at the time, by this news organization.

For the women in this registry, the median time from the last implant to BIA-ALCL diagnosis was 7 years.

The most common presentation was seroma, which occurred in 75.3% of patients, while 21.2% of had a breast tumor mass with or without seroma.

Stage I-II disease was identified in 76.5% of patients, and 21.2% of cases were stage IV. Infiltrative disease was present in 24.7%.

Implant removal with total capsulectomy was performed in 77.6%; 29.4% of women also received chemotherapy, with 11.8% receiving BV-CHP.

A complete response was achieved in 84% of patients who received chemotherapy, while 8% failed to respond. Among the patients who received BV-CHP, 80% achieved a complete response.

After a median follow-up of 28.6 months, 91.8% patients were alive and progression free. All patients treated with BV-CHP were alive and progression free after a median follow-up of 1 year.

Patients with infiltrative disease had a significantly worse 2-year progression-free survival than those with in situ/mixed disease, at 73.8% versus 96.7%, or a hazard ratio for progression of 5.3 (P = .0039).

They also had worse 2-year overall survival, at 78.7% versus 100%, or a hazard ratio for death of 8.5 (P = .0022).

The authors note that these patients with infiltrative disease had significantly worse survival outcomes and may benefit most from BV-CHP.

No funding for the study was declared. Dr. Le Bras reports relationships with Novartis, Celgene, BMS, Takeda, Kite, and Gilead. Other authors declare numerous relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Weekly COVID-19 cases in children topped 1 million for the first time as the cumulative count surpassed 10 million since the start of the pandemic, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

There were 1.15 million cases of COVID-19 reported in children during the week of Jan. 14-20 in the United States, making it the fourth consecutive record-high week and bringing the total number of cases to 10.6 million, the AAP and CHA said in their weekly COVID report. Those 10.6 million child cases represent 18.4% of all cases, and the latest 1.15 million represented 25.5% of all cases for the week.

Regionally, the South had the most cases with over 380,000 for the week of Jan. 14-20, while the West was next with close to 350,000, followed by the Midwest and then the East. Among the states, the largest percent increases – on the order of 30% – came in New England (Massachusetts, Rhode Island, and Vermont), as well as Virginia and California, the AAP and CHA said.

Examining all those cases by vaccination status shows an obvious difference between the Omicron and Delta variants: The fully vaccinated have been hit much harder than before. For the week ending Dec. 25, 2021, the incidence of COVID-19 in children aged 12-17 years was 704 per 100,000 among those were unvaccinated and 384 per 100,000 in those who were fully vaccinated. During the Delta surge in the summer of 2021, the peak rates were 938 (unvaccinated) and 79 (vaccinated), the Centers for Disease Control and Prevention said.

Hospitalizations are also at record levels, but two separate CDC databases seem to show a decline in child admissions over the last available week or so of data, which follows the trend among all ages. The peak among children aged 0-17 years came on Jan. 15, when the rate of new admissions reached 1.25 per 100,000, based on reporting to the CDC from 5,265 hospitals nationwide.

The second database, the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), indicates that children aged 0-4 years had the highest admission rate, 14.5 per 100,000, for the week ending Jan. 8, compared with 5.5 per 100,000 for 12- to 17-year-olds and 2.3 per 100,000 for those aged 5-11 years. COVID-NET covers almost 100 counties in 10 states, along with 4 entire states, and represents about 10% of the U.S. population.

Vaccinations rose briefly in late December and into January to meet the Omicron surge, but the numbers for the latest week show a return to their earlier levels. In children aged 5-11 years, new vaccinations went from 381,000 for the week of Dec. 20-26 to 524,000 for Jan. 3-9, but fell to just 260,000 during Jan. 17-23. The response was a little later for those aged 12-17, with the big week coming Jan. 10-16, but there was still a 38% drop for Jan. 17-23, according to the CDC’s COVID Data Tracker.

Currently, 29.3% of all 5- to 11-year-olds have received at least one dose of the COVID vaccine, and an even 20.0% are fully vaccinated. For children aged 12-17, the corresponding figures are 65.8% and 55.1%, the CDC said.

Statewide vaccination rates vary from Vermont’s high of 61% for those aged 5-11 to 12% for Alabama, Louisiana, and Mississippi, while Hawaii has the highest rate for 12- to 17-year-olds at 92% and Wyoming has the lowest at 39%, the AAP reported.

 

Weekly COVID-19 cases in children topped 1 million for the first time as the cumulative count surpassed 10 million since the start of the pandemic, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

There were 1.15 million cases of COVID-19 reported in children during the week of Jan. 14-20 in the United States, making it the fourth consecutive record-high week and bringing the total number of cases to 10.6 million, the AAP and CHA said in their weekly COVID report. Those 10.6 million child cases represent 18.4% of all cases, and the latest 1.15 million represented 25.5% of all cases for the week.

Regionally, the South had the most cases with over 380,000 for the week of Jan. 14-20, while the West was next with close to 350,000, followed by the Midwest and then the East. Among the states, the largest percent increases – on the order of 30% – came in New England (Massachusetts, Rhode Island, and Vermont), as well as Virginia and California, the AAP and CHA said.

Examining all those cases by vaccination status shows an obvious difference between the Omicron and Delta variants: The fully vaccinated have been hit much harder than before. For the week ending Dec. 25, 2021, the incidence of COVID-19 in children aged 12-17 years was 704 per 100,000 among those were unvaccinated and 384 per 100,000 in those who were fully vaccinated. During the Delta surge in the summer of 2021, the peak rates were 938 (unvaccinated) and 79 (vaccinated), the Centers for Disease Control and Prevention said.

Hospitalizations are also at record levels, but two separate CDC databases seem to show a decline in child admissions over the last available week or so of data, which follows the trend among all ages. The peak among children aged 0-17 years came on Jan. 15, when the rate of new admissions reached 1.25 per 100,000, based on reporting to the CDC from 5,265 hospitals nationwide.

The second database, the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), indicates that children aged 0-4 years had the highest admission rate, 14.5 per 100,000, for the week ending Jan. 8, compared with 5.5 per 100,000 for 12- to 17-year-olds and 2.3 per 100,000 for those aged 5-11 years. COVID-NET covers almost 100 counties in 10 states, along with 4 entire states, and represents about 10% of the U.S. population.

Vaccinations rose briefly in late December and into January to meet the Omicron surge, but the numbers for the latest week show a return to their earlier levels. In children aged 5-11 years, new vaccinations went from 381,000 for the week of Dec. 20-26 to 524,000 for Jan. 3-9, but fell to just 260,000 during Jan. 17-23. The response was a little later for those aged 12-17, with the big week coming Jan. 10-16, but there was still a 38% drop for Jan. 17-23, according to the CDC’s COVID Data Tracker.

Currently, 29.3% of all 5- to 11-year-olds have received at least one dose of the COVID vaccine, and an even 20.0% are fully vaccinated. For children aged 12-17, the corresponding figures are 65.8% and 55.1%, the CDC said.

Statewide vaccination rates vary from Vermont’s high of 61% for those aged 5-11 to 12% for Alabama, Louisiana, and Mississippi, while Hawaii has the highest rate for 12- to 17-year-olds at 92% and Wyoming has the lowest at 39%, the AAP reported.

 

Weekly COVID-19 cases in children topped 1 million for the first time as the cumulative count surpassed 10 million since the start of the pandemic, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

There were 1.15 million cases of COVID-19 reported in children during the week of Jan. 14-20 in the United States, making it the fourth consecutive record-high week and bringing the total number of cases to 10.6 million, the AAP and CHA said in their weekly COVID report. Those 10.6 million child cases represent 18.4% of all cases, and the latest 1.15 million represented 25.5% of all cases for the week.

Regionally, the South had the most cases with over 380,000 for the week of Jan. 14-20, while the West was next with close to 350,000, followed by the Midwest and then the East. Among the states, the largest percent increases – on the order of 30% – came in New England (Massachusetts, Rhode Island, and Vermont), as well as Virginia and California, the AAP and CHA said.

Examining all those cases by vaccination status shows an obvious difference between the Omicron and Delta variants: The fully vaccinated have been hit much harder than before. For the week ending Dec. 25, 2021, the incidence of COVID-19 in children aged 12-17 years was 704 per 100,000 among those were unvaccinated and 384 per 100,000 in those who were fully vaccinated. During the Delta surge in the summer of 2021, the peak rates were 938 (unvaccinated) and 79 (vaccinated), the Centers for Disease Control and Prevention said.

Hospitalizations are also at record levels, but two separate CDC databases seem to show a decline in child admissions over the last available week or so of data, which follows the trend among all ages. The peak among children aged 0-17 years came on Jan. 15, when the rate of new admissions reached 1.25 per 100,000, based on reporting to the CDC from 5,265 hospitals nationwide.

The second database, the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), indicates that children aged 0-4 years had the highest admission rate, 14.5 per 100,000, for the week ending Jan. 8, compared with 5.5 per 100,000 for 12- to 17-year-olds and 2.3 per 100,000 for those aged 5-11 years. COVID-NET covers almost 100 counties in 10 states, along with 4 entire states, and represents about 10% of the U.S. population.

Vaccinations rose briefly in late December and into January to meet the Omicron surge, but the numbers for the latest week show a return to their earlier levels. In children aged 5-11 years, new vaccinations went from 381,000 for the week of Dec. 20-26 to 524,000 for Jan. 3-9, but fell to just 260,000 during Jan. 17-23. The response was a little later for those aged 12-17, with the big week coming Jan. 10-16, but there was still a 38% drop for Jan. 17-23, according to the CDC’s COVID Data Tracker.

Currently, 29.3% of all 5- to 11-year-olds have received at least one dose of the COVID vaccine, and an even 20.0% are fully vaccinated. For children aged 12-17, the corresponding figures are 65.8% and 55.1%, the CDC said.

Statewide vaccination rates vary from Vermont’s high of 61% for those aged 5-11 to 12% for Alabama, Louisiana, and Mississippi, while Hawaii has the highest rate for 12- to 17-year-olds at 92% and Wyoming has the lowest at 39%, the AAP reported.