Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM-3 study

IF 7.6 2区 医学 Q1 HEMATOLOGY
HemaSphere Pub Date : 2024-07-24 DOI:10.1002/hem3.136
Michael H. Tomasson, Shinsuke Iida, Ruben Niesvizky, Mohamad Mohty, Nizar J. Bahlis, Joaquin Martinez-Lopez, Guenther Koehne, Paula Rodriguez-Otero, H. Miles Prince, Andrea Viqueira, Eric Leip, Umberto Conte, Sharon T. Sullivan, Alexander M. Lesokhin
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Lesokhin","doi":"10.1002/hem3.136","DOIUrl":null,"url":null,"abstract":"<p>Targeting B-cell maturation antigen (BCMA) on myeloma cells has led to improved clinical benefit in heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM), including those patients with triple-class exposed disease.<span><sup>1</sup></span> Elranatamab, a humanized BCMA-CD3 bispecific antibody, was approved for the treatment of patients with RRMM based on the results from the registrational MagnetisMM-3 study, which enrolled patients previously treated with at least one immunomodulatory drug, one proteasome inhibitor, and one anti-CD38 monoclonal antibody.<span><sup>2, 3</sup></span> Among BCMA-naive patients (<i>n</i> = 123), treatment with elranatamab led to an objective response rate (ORR) of 61.0%, with 35.0% of patients achieving a complete response (CR) or better.<span><sup>4</sup></span> After a descriptive median follow-up of 14.7 months (data cutoff approximately 14 months after the last patient's initial dose), the median progression-free survival (PFS) and overall survival (OS) had not been reached, making it difficult to contextualize the survival outcomes in the treatment landscape for RRMM.<span><sup>4</sup></span> Here, we report updated results, including Kaplan–Meier estimates of PFS and OS after a longer follow-up.</p><p>As of the data cutoff of March 26, 2024 (approximately 26 months after the last patient's initial dose), with a median follow-up of 28.4 months (95% confidence interval [CI], 28.0–29.0; estimated by reverse Kaplan–Meier), the ORR was 61.0%, with 37.4% of patients achieving CR or better. Among responders, the median duration of response was not yet reached, and the probability of maintaining response at 24 months was 66.9% (95% CI, 54.4–76.7). The median PFS was 17.2 months (95% CI, 9.8–not-estimable [NE]) (Figure 1) and the median OS was 24.6 months (95% CI, 13.4–NE) (Figure 2).</p><p>No new safety signals emerged with longer follow-up. Hematologic adverse events in ≥25% (any grade, maximum grade 3/4) of the patient population included neutropenia (49.6%, 49.6%), anemia (48.8%, 37.4%), thrombocytopenia (31.7%, 23.6%), and lymphopenia (26.8%, 25.2%). Other adverse events of interest observed in patients included infections (70.7%; 42.3% maximum grade 3/4; 6.5% grade 5), cytokine release syndrome (57.7%; all grade ≤2), and immune effector cell–associated neurotoxicity (4.9%; all grade ≤2).</p><p>Elranatamab monotherapy continues to improve survival outcomes without new safety signals. Despite the refractory patient population with a high percentage of patients with poor prognostic features in MagnetisMM-3, the median PFS of 17.2 months and the median OS of 24.6 months observed with additional follow-up are promising among bispecific antibodies currently approved for RRMM. In an analysis of MajesTEC-1 with a median follow-up of 23 months, BCMA-naive patients treated with teclistamab had a median PFS of 11.3 months (95% CI, 8.8–16.4) and a median OS of 21.9 months (95% CI, 15.1–NE).<span><sup>5</sup></span> In the MonumenTAL-1 trial, talquetamab, a bispecific antibody against CD3 and G-protein-coupled receptor, class C, group 5, member D (GPRC5D) showed a median PFS of 7.5 and 11.9 (61% censored) months in the once-weekly and once every 2 weeks dosing cohorts after a median follow-up of 14.9 and 8.6 months, respectively.<span><sup>6</sup></span> The observed safety profile with elranatamab is consistent with that of teclistamab as well as other BCMA-targeted bispecific antibodies.<span><sup>5, 7-10</sup></span></p><p>In conclusion, extended follow-up from the ongoing phase 2 MagnetisMM-3 trial of elranatamab in BCMA-naive patients with heavily pretreated RRMM demonstrated sustained clinical efficacy and no new safety signals.</p><p>All authors were involved in the trial conception/design or the acquisition, analysis, or interpretation of data. 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引用次数: 0

Abstract

Targeting B-cell maturation antigen (BCMA) on myeloma cells has led to improved clinical benefit in heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM), including those patients with triple-class exposed disease.1 Elranatamab, a humanized BCMA-CD3 bispecific antibody, was approved for the treatment of patients with RRMM based on the results from the registrational MagnetisMM-3 study, which enrolled patients previously treated with at least one immunomodulatory drug, one proteasome inhibitor, and one anti-CD38 monoclonal antibody.2, 3 Among BCMA-naive patients (n = 123), treatment with elranatamab led to an objective response rate (ORR) of 61.0%, with 35.0% of patients achieving a complete response (CR) or better.4 After a descriptive median follow-up of 14.7 months (data cutoff approximately 14 months after the last patient's initial dose), the median progression-free survival (PFS) and overall survival (OS) had not been reached, making it difficult to contextualize the survival outcomes in the treatment landscape for RRMM.4 Here, we report updated results, including Kaplan–Meier estimates of PFS and OS after a longer follow-up.

As of the data cutoff of March 26, 2024 (approximately 26 months after the last patient's initial dose), with a median follow-up of 28.4 months (95% confidence interval [CI], 28.0–29.0; estimated by reverse Kaplan–Meier), the ORR was 61.0%, with 37.4% of patients achieving CR or better. Among responders, the median duration of response was not yet reached, and the probability of maintaining response at 24 months was 66.9% (95% CI, 54.4–76.7). The median PFS was 17.2 months (95% CI, 9.8–not-estimable [NE]) (Figure 1) and the median OS was 24.6 months (95% CI, 13.4–NE) (Figure 2).

No new safety signals emerged with longer follow-up. Hematologic adverse events in ≥25% (any grade, maximum grade 3/4) of the patient population included neutropenia (49.6%, 49.6%), anemia (48.8%, 37.4%), thrombocytopenia (31.7%, 23.6%), and lymphopenia (26.8%, 25.2%). Other adverse events of interest observed in patients included infections (70.7%; 42.3% maximum grade 3/4; 6.5% grade 5), cytokine release syndrome (57.7%; all grade ≤2), and immune effector cell–associated neurotoxicity (4.9%; all grade ≤2).

Elranatamab monotherapy continues to improve survival outcomes without new safety signals. Despite the refractory patient population with a high percentage of patients with poor prognostic features in MagnetisMM-3, the median PFS of 17.2 months and the median OS of 24.6 months observed with additional follow-up are promising among bispecific antibodies currently approved for RRMM. In an analysis of MajesTEC-1 with a median follow-up of 23 months, BCMA-naive patients treated with teclistamab had a median PFS of 11.3 months (95% CI, 8.8–16.4) and a median OS of 21.9 months (95% CI, 15.1–NE).5 In the MonumenTAL-1 trial, talquetamab, a bispecific antibody against CD3 and G-protein-coupled receptor, class C, group 5, member D (GPRC5D) showed a median PFS of 7.5 and 11.9 (61% censored) months in the once-weekly and once every 2 weeks dosing cohorts after a median follow-up of 14.9 and 8.6 months, respectively.6 The observed safety profile with elranatamab is consistent with that of teclistamab as well as other BCMA-targeted bispecific antibodies.5, 7-10

In conclusion, extended follow-up from the ongoing phase 2 MagnetisMM-3 trial of elranatamab in BCMA-naive patients with heavily pretreated RRMM demonstrated sustained clinical efficacy and no new safety signals.

All authors were involved in the trial conception/design or the acquisition, analysis, or interpretation of data. All authors contributed to the drafting of the manuscript and approved the final version.

Michael H. Tomasson: consulting or advisory roles for Janssen. Shinsuke Iida: honoraria from Bristol Myers Squibb, Celgene, Janssen, Pfizer, Sanofi, and Takeda; consulting or advisory roles for Janssen, Sanofi, and Takeda; and research funding from AbbVie, Amgen, Bristol Myers Squibb, Caelum Biosciences, Celgene, Daiichi Sankyo, Janssen, Ono, Otsuka, Sanofi, and Takeda. Ruben Niesvizky: consulting or advisory roles for Bristol Myers Squibb, GSK, Janssen, Karyopharm Therapeutics, and Takeda and research funding from Bristol Myers Squibb, GSK, Janssen, Karyopharm Therapeutics, and Takeda. Mohamad Mohty: honoraria from Amgen, Celgene; consulting or advisory roles for Adaptive Biotechnologies, GSK, Jazz Pharmaceuticals, MaaT Pharma, Novartis, Sanofi, and Xenikos; personal fees from Amgen, Astellas, Bristol Myers Squibb, Celgene, Pfizer, Stemline-Menarini and Takeda; and speakers bureau roles for Janssen, Jazz Pharmaceuticals, and Sanofi. Nizar J. Bahlis: honoraria from AbbVie, Amgen, Celgene, Genentech/Roche, GSK, Janssen, Karyopharm Therapeutics, Sanofi, and Takeda; consulting or advisory roles for Amgen, Celgene, Janssen, Karyopharm Therapeutics, Pfizer, Sanofi, and Takeda; personal fees from AbbVie, Amgen, Celgene, Genentech/Roche, GSK, Janssen, Karyopharm Therapeutics, Sanofi, and Takeda; and patents, royalties, and/or other intellectual property interests with Celgene and Janssen. Joaquin Martinez-Lopez: consulting or advisory roles for Bristol Myers Squibb, Janssen, and Novartis; research funding from Astellas and Bristol Myers Squibb; and speakers bureau roles for Bristol Myers Squibb, Janssen-Cilag, and Roche. Paula Rodriguez-Otero: consulting or advisory roles for AbbVie, Bristol Myers Squibb, GSK, Janssen, Pfizer, and Sanofi; personal fees from AbbVie, Celgene, GSK, H3 Biomedicine, Janssen, Pfizer, and Sanofi; travel and accommodations expenses paid by Pfizer; and speakers bureau roles for Bristol Myers Squibb, GSK, Janssen, and Sanofi. Alexander M. Lesokhin: honoraria from iTeos Therapeutics, Janssen, Legend Biotech, Pfizer, Sanofi, and Trillium Therapeutics; consulting or advisory roles for Pfizer, Trillium Therapeutics, and Arcellx; personal fees from iTeos Therapeutics, Janssen, Legend Biotech, Pfizer, Sanofi, and Trillium Therapeutics; research funding from Bristol Myers Squibb, Genentech, Janssen, Pfizer, Sanofi, and Trillium Therapeutics; and patents, royalties and/or other intellectual property interests with Serametrix. Andrea Viqueira, Eric Leip, Umberto Conte, and Sharon T. Sullivan: employment and stock ownership at Pfizer. Guenther Koehne: has no conflicts of interest.

This study was conducted in accordance with the International Council for Harmonisation guidelines for Good Clinical Practice and the principles of the Declaration of Helsinki. The study protocol was approved by local or independent institutional review boards or ethics committees at participating sites.

This study was funded by Pfizer.

Abstract Image

艾拉他单抗对复发或难治性多发性骨髓瘤患者的长期生存率和安全性:MagnetisMM-3研究的最新进展。
Bahlis:AbbVie、Amgen、Celgene、Genentech/Roche、GSK、Janssen、Karyopharm Therapeutics、Sanofi 和 Takeda 的酬金;Amgen、Celgene、Janssen、Karyopharm Therapeutics、Pfizer、Sanofi 和 Takeda 的咨询或顾问角色;来自艾伯维、安进、Celgene、基因泰克/罗氏、葛兰素史克、杨森、Karyopharm Therapeutics、赛诺菲和武田的个人酬金;以及 Celgene 和杨森的专利、特许权使用费和/或其他知识产权利益。Joaquin Martinez-Lopez:担任百时美施贵宝、杨森和诺华的顾问;获得安斯泰来和百时美施贵宝的研究资助;担任百时美施贵宝、杨森-Cilag 和罗氏的发言人。Paula Rodriguez-Otero:担任艾伯维、百时美施贵宝、葛兰素史克、杨森、辉瑞和赛诺菲的顾问;从艾伯维、Celgene、葛兰素史克、H3 Biomedicine、杨森、辉瑞和赛诺菲获得个人酬金;辉瑞支付差旅和住宿费用;担任百时美施贵宝、葛兰素史克、杨森和赛诺菲的发言人。亚历山大-M.Lesokhin:iTeos Therapeutics、杨森、Legend Biotech、辉瑞、赛诺菲和 Trillium Therapeutics 的酬金;辉瑞、Trillium Therapeutics 和 Arcellx 的咨询或顾问角色;iTeos Therapeutics、杨森、Legend Biotech、辉瑞、赛诺菲和 Trillium Therapeutics 的个人酬金;来自百时美施贵宝、基因泰克、杨森、辉瑞、赛诺菲和 Trillium Therapeutics 的研究经费;以及 Serametrix 的专利、特许权使用费和/或其他知识产权利益。Andrea Viqueira、Eric Leip、Umberto Conte 和 Sharon T. Sullivan:在辉瑞公司任职并持有股票。Guenther Koehne:无利益冲突。本研究根据国际协调委员会的《良好临床实践指南》和《赫尔辛基宣言》的原则进行。本研究由辉瑞公司资助。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
HemaSphere
HemaSphere Medicine-Hematology
CiteScore
6.10
自引率
4.50%
发文量
2776
审稿时长
7 weeks
期刊介绍: HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology. In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care. Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.
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