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特立妥单抗治疗复发或难治性多发性骨髓瘤可持久缓解
作者:小柯机器人 发布时间:2022/6/7 17:03:08

法国主宫大学医院Philippe Moreau团队联合美国纪念斯隆·凯特林癌症中心Saad Z. Usmani团队研究了特立妥单抗治疗复发或难治性多发性骨髓瘤的临床1-2期效果。相关论文于2022年6月5日发表于《新英格兰医学杂志》上。

特立妥单抗是一种靶向T细胞表面表达的CD3和骨髓瘤细胞表面表达的B细胞成熟抗原的T细胞重定向双特异性抗体。在该研究的临床1期剂量确定部分,特立妥单抗对复发或难治性多发性骨髓瘤患者显示出良好疗效。

在这项临床1-2期研究中,研究组招募了至少三种治疗方案后复发或难治性骨髓瘤患者,包括三级暴露于免疫调节药物、蛋白酶体抑制剂和抗CD38抗体的患者。患者在接受0.06和0.3 mg/kg体重的递增剂量后,每周皮下注射特立妥单抗(剂量为1.5 mg/kg体重)。主要终点是总体缓解(部分缓解或更好)。

在165名接受特立妥单抗治疗的患者中,77.8%患有三级难治性疾病(此前平均接受过5种治疗方案)。平均随访14.1个月,总有效率为63.0%,其中65名患者(39.4%)完全缓解或更好。共有44例患者(26.7%)无微小残留病灶(MRD);MRD阴性率为46%。中位缓解时间为18.4个月。中位无进展生存期为11.3个月。

常见不良事件包括细胞因子释放综合征(72.1%;3级,0.6%;无4级)、中性粒细胞减少症(70.9%;3或4级,64.2%)、贫血(52.1%;3或4级,37.0%)和血小板减少症(40.0%;3或4级,21.2%)。感染发生较频繁(76.4%;3级或4级,44.8%)。24名患者发生神经毒性事件(14.5%),其中5名患者出现免疫效应细胞相关神经毒性综合征(3.0%;均为1级或2级)。

研究结果表明,特立妥单抗对三级暴露的复发性或难治性多发性骨髓瘤患者有较高的深度和持久缓解率。细胞减少和感染很常见;与T细胞重定向一致的毒性作用大多为1级或2级。

附:英文原文

Title: Teclistamab in Relapsed or Refractory Multiple Myeloma | NEJM

Author: Philippe Moreau, M.D.,, Alfred L. Garfall, M.D.,, Niels W.C.J. van de Donk, M.D., Ph.D.,, Hareth Nahi, M.D., Ph.D.,, Jesús F. San-Miguel, M.D., Ph.D.,, Albert Oriol, M.D., Ph.D.,, Ajay K. Nooka, M.D.,, Thomas Martin, M.D.,, Laura Rosinol, M.D.,, Ajai Chari, M.D.,, Lionel Karlin, M.D.,, Lotfi Benboubker, M.D.,, Maria-Victoria Mateos, M.D., Ph.D.,, Nizar Bahlis, M.D.,, Rakesh Popat, M.D., Ph.D.,, Britta Besemer, M.D.,, Joaquín Martínez-López, M.D., Ph.D,, Surbhi Sidana, M.D.,, Michel Delforge, M.D., Ph.D.,, Lixia Pei, Ph.D.,, Danielle Trancucci, M.Sc.,, Raluca Verona, Ph.D.,, Suzette Girgis, Ph.D.,, Shun X.W. Lin, Ph.D.,, Yunsi Olyslager, M.Sc.,, Mindy Jaffe, M.S.N.,, Clarissa Uhlar, Ph.D.,, Tara Stephenson, Ph.D.,, Rian Van Rampelbergh, M.D.,, Arnob Banerjee, M.D., Ph.D.,, Jenna D. Goldberg, M.D.,, Rachel Kobos, M.D.,, Amrita Krishnan, M.D.,, and Saad Z. Usmani, M.D.

Issue&Volume: 2022-06-05

Abstract:

Background

Teclistamab is a T-cell–redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.

Methods

In this phase 1–2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better).

Results

Among 165 patients who received teclistamab, 77.8% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell–associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2).

Conclusions

Teclistamab resulted in a high rate of deep and durable response in patients with triple-class–exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2.

DOI: 10.1056/NEJMoa2203478

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2203478

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home