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法国巴黎主宫医院Philippe Moreau团队研究了Isatuximab、卡非佐米和地塞米松治疗复发性多发性骨髓瘤的疗效。该成果发表在2021年6月4日出版的《柳叶刀》杂志上。

Isatuximab是一种抗CD38的单克隆抗体，已获批与泊马度胺-地塞米松和卡非佐米-地塞米松联合治疗复发或难治性多发性骨髓瘤。这项临床3期、开放标签研究比较了isatuximab联合卡非佐米-地塞米松和卡非佐米-地塞米松治疗复发性多发性骨髓瘤患者的疗效。

研究组在北美、南美、欧洲和亚太地区16个国家的69个研究中心进行了一项前瞻性、随机、开放、平行组、临床3期研究。招募年龄在18岁以上的复发或难治性多发性骨髓瘤患者，既往接受过1至3次治疗，且血清或尿液中M蛋白可测。患者被随机分配（3：2）至isatuximab+卡非佐米+地塞米松（isatuximab组）或卡非佐米+地塞米松（对照组）治疗。

Isatuximab组患者前4周每周静脉注射isatuximab 10 mg/kg，之后每2周注射一次。两组均接受批准的卡非佐米静脉注射和口服或静脉注射地塞米松。持续治疗直到病情恶化或出现不可接受的毒性。主要终点为无进展生存期，并根据指定的治疗方案在意向治疗人群中进行评估。对所有接受至少一剂治疗的患者进行安全性评估。

2017年11月15日至2019年3月21日，研究组共招募了302名患者，平均接受过两种治疗方案。Isatuximab组179例，对照组123例。与对照组的19.15个月相比，isatuximab组尚未达到中位无进展生存期，风险比为0.53。Isatuximab组177例患者中136例（77%）出现3级及以上的治疗性不良事件（TEAE），对照组122例患者中82例（67%）；两组中分别有105例（59%）和70例（57%）患者发生严重TEAE，且分别导致15例（8%）和17例（14%）患者停药。在研究治疗期间，isatuximab组有6例（3%）患者发生了致命TEAE，对照组有4例（3%）。

研究结果表明，卡非佐米-地塞米松联合isatuximab治疗可显著改善复发性多发性骨髓瘤患者的无进展生存期和缓解深度。

附：英文原文

Title: Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial

Author: Philippe Moreau, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Kwee Yong, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan pika, Ross Baker, Kihyun Kim, Gracia Martinez, Chang-Ki Min, Ludek Pour, Xavier Leleu, Albert Oriol, Youngil Koh, Kenshi Suzuki, Marie-Laure Risse, Gaelle Asset, Sandrine Macé, Thomas Martin, Philippe Moreau, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Kwee Yong, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Spicka, Ross Baker, Kim Kihyun, Gracia Martinez, Min Chang-Ki, Ludek Pour, Xavier Leleu, Albert Oriol, Koh Youngil, Kenshi Suzuki, Tom Martin, Hang Quach, Andrew Lim, Helen Crowther, Hanlon Sia, Cyrille Hulin, Mohamad Mohty, Gabor Mikala, Zsolt Nagy, Marta Reinoso Segura, Laura Rosinol, Munci Yagci, Mehmet Turgut, Mamta Garg, Gurdeep Parmar, Brad Augustson, Nelson Castro, Edvan Crusoe, Tomas Pika, Sosana Delimpasi, Kenichi Ishizawa, Anup George, Tatiana Konstantinova, Javier De La Rubia, Kim Sung-Hyun, Angelo Maiolino, Anthony Reiman, Richard LeBlanc, Shigeki Ito, Junji Tanaka, Alexander Luchinin, Irina Kryuchkova, Joaquin Martinez, Jesse Shustik, Lionel Karlin, Anargyros Symeonidis, Miklos Egyed, Mario Petrini, Michele Cavo, Michihiro Uchiyama, Hilary Blacklock, Mutlu Arat, James Griffin, Hannah Hunter, Tonda Buck, Achilles Anagnostopoulos, Konstantinos Konstantopoulos, Tamas Masszi, Sara Bringhen, Barbara Gamberi, Yawara Kawano, Kim Jin Seok, Hakan Ozdogu, Fahir Ozkalemkas

Issue&Volume: 2021-06-04

Abstract:

Background

Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide–dexamethasone and carfilzomib–dexamethasone for relapsed or refractory multiple myeloma. This phase 3, open-label study compared the efficacy of isatuximab plus carfilzomib–dexamethasone versus carfilzomib–dexamethasone in patients with relapsed multiple myeloma.

Methods

This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple myeloma aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib–dexamethasone (isatuximab group) or carfilzomib–dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received the approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285.

Findings

Between Nov 15, 2017, and March 21, 2019, 302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19·15 months (95% CI 15·77–not reached) in the control group, with a hazard ratio of 0·53 (99% CI 0·32–0·89; one-sided p=0·0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEAEs led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEAEs during study treatment occurred in six (3%) versus four (3%) patients.

Interpretation

The addition of isatuximab to carfilzomib–dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population.

DOI: 10.1016/S0140-6736(21)00592-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00592-4/fulltext

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