Breast Cancer ICYMI

Key clinical point: Patients with breast cancer (BC) treated with standard chemotherapy during pregnancy show comparable prognosis to young nonpregnant patients with BC, supporting chemotherapy initiation in pregnant women with BC as indicated.

Major finding: Median follow-up was 66.3 months. Disease-free survival (hazard ratio [HR] 1.024; P = .830) and overall survival (HR 1.082; P = .592) were not significantly different between pregnant and nonpregnant patients receiving chemotherapy.

Study details: Findings are from a large cohort study including 2081 nonpregnant women aged <45 years and 662 pregnant women, all of whom were diagnosed with stage I-III BC and received standard chemotherapy.

Disclosures: This study was funded by German Breast Group and other sources. Some authors declared receiving grants, honoraria, personal fees, or speaking fees from several sources.

Source: Amant F et al. Outcome of breast cancer patients treated with chemotherapy during pregnancy compared with non-pregnant controls. Eur J Cancer. 2022;170:54-63 (May 17). Doi: 10.1016/j.ejca.2022.04.014

Key clinical point: Patients with breast cancer (BC) treated with standard chemotherapy during pregnancy show comparable prognosis to young nonpregnant patients with BC, supporting chemotherapy initiation in pregnant women with BC as indicated.

Major finding: Median follow-up was 66.3 months. Disease-free survival (hazard ratio [HR] 1.024; P = .830) and overall survival (HR 1.082; P = .592) were not significantly different between pregnant and nonpregnant patients receiving chemotherapy.

Study details: Findings are from a large cohort study including 2081 nonpregnant women aged <45 years and 662 pregnant women, all of whom were diagnosed with stage I-III BC and received standard chemotherapy.

Disclosures: This study was funded by German Breast Group and other sources. Some authors declared receiving grants, honoraria, personal fees, or speaking fees from several sources.

Source: Amant F et al. Outcome of breast cancer patients treated with chemotherapy during pregnancy compared with non-pregnant controls. Eur J Cancer. 2022;170:54-63 (May 17). Doi: 10.1016/j.ejca.2022.04.014

Key clinical point: Patients with breast cancer (BC) treated with standard chemotherapy during pregnancy show comparable prognosis to young nonpregnant patients with BC, supporting chemotherapy initiation in pregnant women with BC as indicated.

Major finding: Median follow-up was 66.3 months. Disease-free survival (hazard ratio [HR] 1.024; P = .830) and overall survival (HR 1.082; P = .592) were not significantly different between pregnant and nonpregnant patients receiving chemotherapy.

Study details: Findings are from a large cohort study including 2081 nonpregnant women aged <45 years and 662 pregnant women, all of whom were diagnosed with stage I-III BC and received standard chemotherapy.

Disclosures: This study was funded by German Breast Group and other sources. Some authors declared receiving grants, honoraria, personal fees, or speaking fees from several sources.

Source: Amant F et al. Outcome of breast cancer patients treated with chemotherapy during pregnancy compared with non-pregnant controls. Eur J Cancer. 2022;170:54-63 (May 17). Doi: 10.1016/j.ejca.2022.04.014

Key clinical point: Male-origin infertility was associated with an increased risk for breast cancer (BC) in men.

Major finding: Risk for BC was significantly higher in men diagnosed with infertility (odds ratio [OR] 2.03; P = .01), those diagnosed with infertility or low sperm count (OR 2.17; P = .004), and those who had not fathered any children (OR 1.50; P < .001).

Study details: Findings are from a case-control study including 1998 men diagnosed with in situ or invasive BC at <80 years of age and 1597 matched male controls.

Disclosures: This study was supported by Breast Cancer Now, formerly Breakthrough Breast Cancer, and the John Tridgell family. The authors declared no conflicts of interest.

Source: Swerdlow AJ et al. Infertility and risk of breast cancer in men: a national case–control study in England and Wales. Breast Cancer Res. 2022;24:29 (May 17). Doi: 10.1186/s13058-022-01517-z

Key clinical point: Male-origin infertility was associated with an increased risk for breast cancer (BC) in men.

Major finding: Risk for BC was significantly higher in men diagnosed with infertility (odds ratio [OR] 2.03; P = .01), those diagnosed with infertility or low sperm count (OR 2.17; P = .004), and those who had not fathered any children (OR 1.50; P < .001).

Study details: Findings are from a case-control study including 1998 men diagnosed with in situ or invasive BC at <80 years of age and 1597 matched male controls.

Disclosures: This study was supported by Breast Cancer Now, formerly Breakthrough Breast Cancer, and the John Tridgell family. The authors declared no conflicts of interest.

Source: Swerdlow AJ et al. Infertility and risk of breast cancer in men: a national case–control study in England and Wales. Breast Cancer Res. 2022;24:29 (May 17). Doi: 10.1186/s13058-022-01517-z

Key clinical point: Male-origin infertility was associated with an increased risk for breast cancer (BC) in men.

Major finding: Risk for BC was significantly higher in men diagnosed with infertility (odds ratio [OR] 2.03; P = .01), those diagnosed with infertility or low sperm count (OR 2.17; P = .004), and those who had not fathered any children (OR 1.50; P < .001).

Study details: Findings are from a case-control study including 1998 men diagnosed with in situ or invasive BC at <80 years of age and 1597 matched male controls.

Disclosures: This study was supported by Breast Cancer Now, formerly Breakthrough Breast Cancer, and the John Tridgell family. The authors declared no conflicts of interest.

Source: Swerdlow AJ et al. Infertility and risk of breast cancer in men: a national case–control study in England and Wales. Breast Cancer Res. 2022;24:29 (May 17). Doi: 10.1186/s13058-022-01517-z

Key clinical point: Patients who received adjuvant radiotherapy for breast cancer (BC) experienced a significant reduction in radiation-induced dermatitis (RID) incidence and severity after the prophylactic use of epigallocatechin-3-gallate (EGCG) solution.

Major finding: Incidence rates of grade ≥2 RID (50.5% vs. 72.2%; P = .008), the mean RID index of patients (5.22 vs. 6.21; P < .001), and RID-related symptoms, such as pain (P = .03), burning sensation (P = .001), itching (P < .001), and tenderness (P = .002), were significantly lower in the EGCG vs. placebo group. No severe EGCG solution/placebo-related adverse events were observed.

Study details: Findings are from a double-blind, phase 2 study including 165 women with histologically confirmed BC who received postoperative radiotherapy and were randomly assigned to receive EGCG solution or placebo.

Disclosures: Z Zhou, J Yu, and H Zhao received funding from the National Natural Science Foundation of China, Jinan Science and Technology Plan Project, and other sources. The authors declared no conflicts of interest.

Source: Zhao H et al. Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy: A double-blind, placebo-controlled, phase 2 randomized clinical trial. JAMA Dermatol. 2022 (Jun 1). Doi: 10.1001/jamadermatol.2022.1736

Key clinical point: Patients who received adjuvant radiotherapy for breast cancer (BC) experienced a significant reduction in radiation-induced dermatitis (RID) incidence and severity after the prophylactic use of epigallocatechin-3-gallate (EGCG) solution.

Major finding: Incidence rates of grade ≥2 RID (50.5% vs. 72.2%; P = .008), the mean RID index of patients (5.22 vs. 6.21; P < .001), and RID-related symptoms, such as pain (P = .03), burning sensation (P = .001), itching (P < .001), and tenderness (P = .002), were significantly lower in the EGCG vs. placebo group. No severe EGCG solution/placebo-related adverse events were observed.

Study details: Findings are from a double-blind, phase 2 study including 165 women with histologically confirmed BC who received postoperative radiotherapy and were randomly assigned to receive EGCG solution or placebo.

Disclosures: Z Zhou, J Yu, and H Zhao received funding from the National Natural Science Foundation of China, Jinan Science and Technology Plan Project, and other sources. The authors declared no conflicts of interest.

Source: Zhao H et al. Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy: A double-blind, placebo-controlled, phase 2 randomized clinical trial. JAMA Dermatol. 2022 (Jun 1). Doi: 10.1001/jamadermatol.2022.1736

Key clinical point: Patients who received adjuvant radiotherapy for breast cancer (BC) experienced a significant reduction in radiation-induced dermatitis (RID) incidence and severity after the prophylactic use of epigallocatechin-3-gallate (EGCG) solution.

Major finding: Incidence rates of grade ≥2 RID (50.5% vs. 72.2%; P = .008), the mean RID index of patients (5.22 vs. 6.21; P < .001), and RID-related symptoms, such as pain (P = .03), burning sensation (P = .001), itching (P < .001), and tenderness (P = .002), were significantly lower in the EGCG vs. placebo group. No severe EGCG solution/placebo-related adverse events were observed.

Study details: Findings are from a double-blind, phase 2 study including 165 women with histologically confirmed BC who received postoperative radiotherapy and were randomly assigned to receive EGCG solution or placebo.

Disclosures: Z Zhou, J Yu, and H Zhao received funding from the National Natural Science Foundation of China, Jinan Science and Technology Plan Project, and other sources. The authors declared no conflicts of interest.

Source: Zhao H et al. Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy: A double-blind, placebo-controlled, phase 2 randomized clinical trial. JAMA Dermatol. 2022 (Jun 1). Doi: 10.1001/jamadermatol.2022.1736

Key clinical point: Etirinotecan pegol failed to prolong survival compared with chemotherapy in patients with metastatic breast cancer (BC) and stable pretreated brain metastases (BM).

Major finding: The median overall survival (hazard ratio [HR] 0.90; P = .60) and median progression-free survival for non-central nervous system (CNS; HR 0.72; P = .18) or CNS (HR 0.59; P = .07) metastases were similar in the etirinotecan pegol and chemotherapy groups, with overall safety profiles of the two treatments being largely comparable.

Study details: Findings are from the phase 3 ATTAIN study including 178 patients with metastatic BC and a history of stable pretreated BM who were randomly assigned to receive etirinotecan pegol or chemotherapy.

Disclosures: This study was funded by Nektar Therapeutics. Dr. Hoch and Dr. Tagliaferri declared being employees of Nektar Therapeutics, and the other authors reported ties with several sources, including Nektar Therapeutics.

Source: Tripathy D et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: Final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022 (May 12). Doi: 10.1001/jamaoncol.2022.0514

Key clinical point: Etirinotecan pegol failed to prolong survival compared with chemotherapy in patients with metastatic breast cancer (BC) and stable pretreated brain metastases (BM).

Major finding: The median overall survival (hazard ratio [HR] 0.90; P = .60) and median progression-free survival for non-central nervous system (CNS; HR 0.72; P = .18) or CNS (HR 0.59; P = .07) metastases were similar in the etirinotecan pegol and chemotherapy groups, with overall safety profiles of the two treatments being largely comparable.

Study details: Findings are from the phase 3 ATTAIN study including 178 patients with metastatic BC and a history of stable pretreated BM who were randomly assigned to receive etirinotecan pegol or chemotherapy.

Disclosures: This study was funded by Nektar Therapeutics. Dr. Hoch and Dr. Tagliaferri declared being employees of Nektar Therapeutics, and the other authors reported ties with several sources, including Nektar Therapeutics.

Source: Tripathy D et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: Final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022 (May 12). Doi: 10.1001/jamaoncol.2022.0514

Key clinical point: Etirinotecan pegol failed to prolong survival compared with chemotherapy in patients with metastatic breast cancer (BC) and stable pretreated brain metastases (BM).

Major finding: The median overall survival (hazard ratio [HR] 0.90; P = .60) and median progression-free survival for non-central nervous system (CNS; HR 0.72; P = .18) or CNS (HR 0.59; P = .07) metastases were similar in the etirinotecan pegol and chemotherapy groups, with overall safety profiles of the two treatments being largely comparable.

Study details: Findings are from the phase 3 ATTAIN study including 178 patients with metastatic BC and a history of stable pretreated BM who were randomly assigned to receive etirinotecan pegol or chemotherapy.

Disclosures: This study was funded by Nektar Therapeutics. Dr. Hoch and Dr. Tagliaferri declared being employees of Nektar Therapeutics, and the other authors reported ties with several sources, including Nektar Therapeutics.

Source: Tripathy D et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: Final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022 (May 12). Doi: 10.1001/jamaoncol.2022.0514

Key clinical point: Adjuvant breast intensity-modulated radiotherapy (IMRT) in the prone vs. supine position was less toxic in women with large breast size and early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS).

Major finding: IMRT in the supine vs. prone position was significantly associated with higher rates of desquamation anywhere in the breast and grade 3 desquamation in the overall cohort (odds ratio [OR] 1.78; P = .002, and OR 2.09; P < .001, respectively) and among women receiving extended fractionation (OR 1.92 and OR 2.76, respectively; both P < .001). The quality of life outcomes were similar between both treatment arms.

Study details: This phase 3 study included 357 women with large breast size and early-stage BC who underwent BCS and were randomly assigned to receive adjuvant IMRT in the supine or prone position.

Disclosures: This study was supported by Canadian Cancer Society. Dr. Rakovitch declared receiving grants and personal fees from some sources, and Dr. Pignol declared being employed by Accuray Inc.

Source: Vesprini D et al. Effect of supine vs prone breast radiotherapy on acute toxic effects of the skin among women with large breast size: A randomized clinical trial. JAMA Oncol. 2022 (May 26). Doi: 10.1001/jamaoncol.2022.1479

Key clinical point: Adjuvant breast intensity-modulated radiotherapy (IMRT) in the prone vs. supine position was less toxic in women with large breast size and early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS).

Major finding: IMRT in the supine vs. prone position was significantly associated with higher rates of desquamation anywhere in the breast and grade 3 desquamation in the overall cohort (odds ratio [OR] 1.78; P = .002, and OR 2.09; P < .001, respectively) and among women receiving extended fractionation (OR 1.92 and OR 2.76, respectively; both P < .001). The quality of life outcomes were similar between both treatment arms.

Study details: This phase 3 study included 357 women with large breast size and early-stage BC who underwent BCS and were randomly assigned to receive adjuvant IMRT in the supine or prone position.

Disclosures: This study was supported by Canadian Cancer Society. Dr. Rakovitch declared receiving grants and personal fees from some sources, and Dr. Pignol declared being employed by Accuray Inc.

Source: Vesprini D et al. Effect of supine vs prone breast radiotherapy on acute toxic effects of the skin among women with large breast size: A randomized clinical trial. JAMA Oncol. 2022 (May 26). Doi: 10.1001/jamaoncol.2022.1479

Key clinical point: Adjuvant breast intensity-modulated radiotherapy (IMRT) in the prone vs. supine position was less toxic in women with large breast size and early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS).

Major finding: IMRT in the supine vs. prone position was significantly associated with higher rates of desquamation anywhere in the breast and grade 3 desquamation in the overall cohort (odds ratio [OR] 1.78; P = .002, and OR 2.09; P < .001, respectively) and among women receiving extended fractionation (OR 1.92 and OR 2.76, respectively; both P < .001). The quality of life outcomes were similar between both treatment arms.

Study details: This phase 3 study included 357 women with large breast size and early-stage BC who underwent BCS and were randomly assigned to receive adjuvant IMRT in the supine or prone position.

Disclosures: This study was supported by Canadian Cancer Society. Dr. Rakovitch declared receiving grants and personal fees from some sources, and Dr. Pignol declared being employed by Accuray Inc.

Source: Vesprini D et al. Effect of supine vs prone breast radiotherapy on acute toxic effects of the skin among women with large breast size: A randomized clinical trial. JAMA Oncol. 2022 (May 26). Doi: 10.1001/jamaoncol.2022.1479

Key clinical point: Elacestrant significantly improved progression-free survival (PFS) compared with standard-of-care (SOC) endocrine monotherapy in previously treated patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC) with a manageable safety.

Major finding: Elacestrant vs. SOC prolonged PFS in the overall cohort (hazard ratio [HR] 0.70; P = .002) and in patients with estrogen receptor 1 mutation (HR 0.55; P = .0005). Grade 3/4 adverse events occurred in 27.0% vs. 20.5% of patients receiving elacestrant vs. SOC therapy, respectively.

Study details: Findings are from the phase 3 EMERALD study including 477 patients with ER+/HER2− metastatic BC who progressed after the first- or second-line treatment with endocrine therapy + cyclin-dependent kinase 4/6 inhibitor and ≤1 rounds of chemotherapy treatment and were randomly assigned to receive elacestrant or SOC endocrine monotherapy.

Disclosures: This study was sponsored by Radius Health, Inc. The authors declared owning stock options or patents, receiving research funding, travel, accommodation expenses, or honoraria from, or serving as consultants, advisors, and in speakers’ bureaus for several sources, including Radius Health.

Source: Bidard FC et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Results from the randomized phase III EMERALD Trial. J Clin Oncol. 2022 (May 18). Doi: 10.1200/JCO.22.00338

Key clinical point: Elacestrant significantly improved progression-free survival (PFS) compared with standard-of-care (SOC) endocrine monotherapy in previously treated patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC) with a manageable safety.

Major finding: Elacestrant vs. SOC prolonged PFS in the overall cohort (hazard ratio [HR] 0.70; P = .002) and in patients with estrogen receptor 1 mutation (HR 0.55; P = .0005). Grade 3/4 adverse events occurred in 27.0% vs. 20.5% of patients receiving elacestrant vs. SOC therapy, respectively.

Study details: Findings are from the phase 3 EMERALD study including 477 patients with ER+/HER2− metastatic BC who progressed after the first- or second-line treatment with endocrine therapy + cyclin-dependent kinase 4/6 inhibitor and ≤1 rounds of chemotherapy treatment and were randomly assigned to receive elacestrant or SOC endocrine monotherapy.

Disclosures: This study was sponsored by Radius Health, Inc. The authors declared owning stock options or patents, receiving research funding, travel, accommodation expenses, or honoraria from, or serving as consultants, advisors, and in speakers’ bureaus for several sources, including Radius Health.

Source: Bidard FC et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Results from the randomized phase III EMERALD Trial. J Clin Oncol. 2022 (May 18). Doi: 10.1200/JCO.22.00338

Key clinical point: Elacestrant significantly improved progression-free survival (PFS) compared with standard-of-care (SOC) endocrine monotherapy in previously treated patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC) with a manageable safety.

Major finding: Elacestrant vs. SOC prolonged PFS in the overall cohort (hazard ratio [HR] 0.70; P = .002) and in patients with estrogen receptor 1 mutation (HR 0.55; P = .0005). Grade 3/4 adverse events occurred in 27.0% vs. 20.5% of patients receiving elacestrant vs. SOC therapy, respectively.

Study details: Findings are from the phase 3 EMERALD study including 477 patients with ER+/HER2− metastatic BC who progressed after the first- or second-line treatment with endocrine therapy + cyclin-dependent kinase 4/6 inhibitor and ≤1 rounds of chemotherapy treatment and were randomly assigned to receive elacestrant or SOC endocrine monotherapy.

Disclosures: This study was sponsored by Radius Health, Inc. The authors declared owning stock options or patents, receiving research funding, travel, accommodation expenses, or honoraria from, or serving as consultants, advisors, and in speakers’ bureaus for several sources, including Radius Health.

Source: Bidard FC et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Results from the randomized phase III EMERALD Trial. J Clin Oncol. 2022 (May 18). Doi: 10.1200/JCO.22.00338

Key clinical point: In patients with high-risk operable breast cancer (BC) and without diabetes, adding metformin to standard BC treatment did not improve the invasive disease-free survival (iDFS) rate, regardless of estrogen receptor/progesterone receptor (ER/PgR) status.

Major finding: The incidence rates of iDFS events were similar between the metformin and placebo groups in patients with ER/PgR+ BC (2.78 vs. 2.74 per 100 patient-years; P = .93) and ER/PgR− BC (3.58 vs. 3.60 per 100 patient-years; P = .92). Grade ≥3 nonhematological adverse events were more frequent in the metformin vs. placebo group (21.5% vs. 17.5%; P = .003).

Study details: Findings are from the phase 3 MA.32 study including 3649 patients with high-risk operable BC and without diabetes who were randomly assigned to receive metformin or placebo after undergoing complete resection.

Disclosures: This study was funded by the Canadian Cancer Society Research Institute and other sources. The authors declared serving on advisory boards, as consultants, or were employees or received grants, nonfinancial support, or travel expenses from several sources.

Source: Goodwin PJ et al. Effect of metformin vs placebo on invasive disease–free survival in patients with breast cancer: The MA.32 Randomized Clinical Trial. JAMA. 2022;327(20):1963–1973 (May 24). Doi: 10.1001/jama.2022.6147

Key clinical point: In patients with high-risk operable breast cancer (BC) and without diabetes, adding metformin to standard BC treatment did not improve the invasive disease-free survival (iDFS) rate, regardless of estrogen receptor/progesterone receptor (ER/PgR) status.

Major finding: The incidence rates of iDFS events were similar between the metformin and placebo groups in patients with ER/PgR+ BC (2.78 vs. 2.74 per 100 patient-years; P = .93) and ER/PgR− BC (3.58 vs. 3.60 per 100 patient-years; P = .92). Grade ≥3 nonhematological adverse events were more frequent in the metformin vs. placebo group (21.5% vs. 17.5%; P = .003).

Study details: Findings are from the phase 3 MA.32 study including 3649 patients with high-risk operable BC and without diabetes who were randomly assigned to receive metformin or placebo after undergoing complete resection.

Disclosures: This study was funded by the Canadian Cancer Society Research Institute and other sources. The authors declared serving on advisory boards, as consultants, or were employees or received grants, nonfinancial support, or travel expenses from several sources.

Source: Goodwin PJ et al. Effect of metformin vs placebo on invasive disease–free survival in patients with breast cancer: The MA.32 Randomized Clinical Trial. JAMA. 2022;327(20):1963–1973 (May 24). Doi: 10.1001/jama.2022.6147

Key clinical point: In patients with high-risk operable breast cancer (BC) and without diabetes, adding metformin to standard BC treatment did not improve the invasive disease-free survival (iDFS) rate, regardless of estrogen receptor/progesterone receptor (ER/PgR) status.

Major finding: The incidence rates of iDFS events were similar between the metformin and placebo groups in patients with ER/PgR+ BC (2.78 vs. 2.74 per 100 patient-years; P = .93) and ER/PgR− BC (3.58 vs. 3.60 per 100 patient-years; P = .92). Grade ≥3 nonhematological adverse events were more frequent in the metformin vs. placebo group (21.5% vs. 17.5%; P = .003).

Study details: Findings are from the phase 3 MA.32 study including 3649 patients with high-risk operable BC and without diabetes who were randomly assigned to receive metformin or placebo after undergoing complete resection.

Disclosures: This study was funded by the Canadian Cancer Society Research Institute and other sources. The authors declared serving on advisory boards, as consultants, or were employees or received grants, nonfinancial support, or travel expenses from several sources.

Source: Goodwin PJ et al. Effect of metformin vs placebo on invasive disease–free survival in patients with breast cancer: The MA.32 Randomized Clinical Trial. JAMA. 2022;327(20):1963–1973 (May 24). Doi: 10.1001/jama.2022.6147

Key clinical point: The combination of camrelizumab, apatinib, and eribulin demonstrated a favorable efficacy and a manageable safety profile in patients with heavily pretreated advanced triple negative breast cancer (TNBC).

Major finding: The objective response rate (ORR), disease control rate, and median progression-free survival in the overall cohort were 37.0% (95% CI 23.2%-52.5%), 87.0% (95% CI 73.7%-95.1%), and 8.1 months (95% CI 4.6-10.3 months), respectively, whereas the ORR in patients who progressed on previous treatment with checkpoint inhibitor + chemotherapy was 25.0% (95% CI 3.2%-65.1%). Grade 3/4 treatment-related adverse events occurred in 41.3% of patients.

Study details: Findings are from a multicenter, phase 2 study including 46 patients with pretreated advanced TNBC who received camrelizumab on day 1, apatinib daily, and eribulin on days 1 and 8 of a 21-day cycle.

Disclosures: This work was supported by grants from the Natural Science Foundation of China, Guangdong Science and Technology Department, and other sources. The authors declared no conflicts of interest.

Source: Liu J et al. Multicenter phase II trial of camrelizumab combined with apatinib and eribulin in heavily pretreated patients with advanced triple-negative breast cancer. Nat Commun. 2022;13:3011 (May 31). Doi: 10.1038/s41467-022-30569-0

Key clinical point: The combination of camrelizumab, apatinib, and eribulin demonstrated a favorable efficacy and a manageable safety profile in patients with heavily pretreated advanced triple negative breast cancer (TNBC).

Major finding: The objective response rate (ORR), disease control rate, and median progression-free survival in the overall cohort were 37.0% (95% CI 23.2%-52.5%), 87.0% (95% CI 73.7%-95.1%), and 8.1 months (95% CI 4.6-10.3 months), respectively, whereas the ORR in patients who progressed on previous treatment with checkpoint inhibitor + chemotherapy was 25.0% (95% CI 3.2%-65.1%). Grade 3/4 treatment-related adverse events occurred in 41.3% of patients.

Study details: Findings are from a multicenter, phase 2 study including 46 patients with pretreated advanced TNBC who received camrelizumab on day 1, apatinib daily, and eribulin on days 1 and 8 of a 21-day cycle.

Disclosures: This work was supported by grants from the Natural Science Foundation of China, Guangdong Science and Technology Department, and other sources. The authors declared no conflicts of interest.

Source: Liu J et al. Multicenter phase II trial of camrelizumab combined with apatinib and eribulin in heavily pretreated patients with advanced triple-negative breast cancer. Nat Commun. 2022;13:3011 (May 31). Doi: 10.1038/s41467-022-30569-0

Key clinical point: The combination of camrelizumab, apatinib, and eribulin demonstrated a favorable efficacy and a manageable safety profile in patients with heavily pretreated advanced triple negative breast cancer (TNBC).

Major finding: The objective response rate (ORR), disease control rate, and median progression-free survival in the overall cohort were 37.0% (95% CI 23.2%-52.5%), 87.0% (95% CI 73.7%-95.1%), and 8.1 months (95% CI 4.6-10.3 months), respectively, whereas the ORR in patients who progressed on previous treatment with checkpoint inhibitor + chemotherapy was 25.0% (95% CI 3.2%-65.1%). Grade 3/4 treatment-related adverse events occurred in 41.3% of patients.

Study details: Findings are from a multicenter, phase 2 study including 46 patients with pretreated advanced TNBC who received camrelizumab on day 1, apatinib daily, and eribulin on days 1 and 8 of a 21-day cycle.

Disclosures: This work was supported by grants from the Natural Science Foundation of China, Guangdong Science and Technology Department, and other sources. The authors declared no conflicts of interest.

Source: Liu J et al. Multicenter phase II trial of camrelizumab combined with apatinib and eribulin in heavily pretreated patients with advanced triple-negative breast cancer. Nat Commun. 2022;13:3011 (May 31). Doi: 10.1038/s41467-022-30569-0

Key clinical point: Adding denosumab to anthracycline/taxane-based neoadjuvant chemotherapy (NACT) did not improve pathological complete response (pCR) rates, but a weekly vs. every-3-week nanoparticle albumin-bound (nab)-paclitaxel regimen improved pCR rates in patients with early breast cancer (BC), although the toxicity was higher.

Major finding: The addition of denosumab did not improve pCR rates (P = .61). However, a weekly vs. every-3-week nab-paclitaxel regimen resulted in a higher pCR rate (odds ratio [OR] 1.27; 90% CI 1.00-1.62) in the overall population and in patients with triple-negative BC (OR 1.52; 90% CI 1.05-2.21), but the grade 3-4 nonhematologic adverse event frequency was higher (P = .004).

Study details: Findings are from the 2 × 2 phase 2b, GeparX trial including 780 patients with primary BC who were randomly assigned to receive NACT with or without denosumab and a weekly or every-3-week nab-paclitaxel regimen.

Disclosures: The study was sponsored by the German Breast Group. The authors declared holding patents or receiving personal fees, honoraria, grants, trial funding, nonfinancial support, or travel support from several sources.

Source: Blohmer JU et al. Effect of denosumab added to 2 different nab-paclitaxel regimens as neoadjuvant therapy in patients with primary breast cancer: The GeparX 2 × 2 randomized clinical trial. JAMA Oncol. 2022 (May 19). Doi: 10.1001/jamaoncol.2022.1059

Key clinical point: Adding denosumab to anthracycline/taxane-based neoadjuvant chemotherapy (NACT) did not improve pathological complete response (pCR) rates, but a weekly vs. every-3-week nanoparticle albumin-bound (nab)-paclitaxel regimen improved pCR rates in patients with early breast cancer (BC), although the toxicity was higher.

Major finding: The addition of denosumab did not improve pCR rates (P = .61). However, a weekly vs. every-3-week nab-paclitaxel regimen resulted in a higher pCR rate (odds ratio [OR] 1.27; 90% CI 1.00-1.62) in the overall population and in patients with triple-negative BC (OR 1.52; 90% CI 1.05-2.21), but the grade 3-4 nonhematologic adverse event frequency was higher (P = .004).

Study details: Findings are from the 2 × 2 phase 2b, GeparX trial including 780 patients with primary BC who were randomly assigned to receive NACT with or without denosumab and a weekly or every-3-week nab-paclitaxel regimen.

Disclosures: The study was sponsored by the German Breast Group. The authors declared holding patents or receiving personal fees, honoraria, grants, trial funding, nonfinancial support, or travel support from several sources.

Source: Blohmer JU et al. Effect of denosumab added to 2 different nab-paclitaxel regimens as neoadjuvant therapy in patients with primary breast cancer: The GeparX 2 × 2 randomized clinical trial. JAMA Oncol. 2022 (May 19). Doi: 10.1001/jamaoncol.2022.1059

Key clinical point: Adding denosumab to anthracycline/taxane-based neoadjuvant chemotherapy (NACT) did not improve pathological complete response (pCR) rates, but a weekly vs. every-3-week nanoparticle albumin-bound (nab)-paclitaxel regimen improved pCR rates in patients with early breast cancer (BC), although the toxicity was higher.

Major finding: The addition of denosumab did not improve pCR rates (P = .61). However, a weekly vs. every-3-week nab-paclitaxel regimen resulted in a higher pCR rate (odds ratio [OR] 1.27; 90% CI 1.00-1.62) in the overall population and in patients with triple-negative BC (OR 1.52; 90% CI 1.05-2.21), but the grade 3-4 nonhematologic adverse event frequency was higher (P = .004).

Study details: Findings are from the 2 × 2 phase 2b, GeparX trial including 780 patients with primary BC who were randomly assigned to receive NACT with or without denosumab and a weekly or every-3-week nab-paclitaxel regimen.

Disclosures: The study was sponsored by the German Breast Group. The authors declared holding patents or receiving personal fees, honoraria, grants, trial funding, nonfinancial support, or travel support from several sources.

Source: Blohmer JU et al. Effect of denosumab added to 2 different nab-paclitaxel regimens as neoadjuvant therapy in patients with primary breast cancer: The GeparX 2 × 2 randomized clinical trial. JAMA Oncol. 2022 (May 19). Doi: 10.1001/jamaoncol.2022.1059

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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