美国纽约纪念斯隆凯特琳癌症中心Sergio Giralt团队比较了ide-cel或标准方案治疗复发难治性多发性骨髓瘤的疗效与安全性。该研究于2023年2月10日发表在《新英格兰医学杂志》上。

三级暴露的复发难治性多发性骨髓瘤患者生存率较差。Idecabtagene vicleucel（ide-cel） 是一种B细胞成熟抗原导向的嵌合抗原受体（CAR）T细胞疗法，此前在大量预处理的复发和难治性多发性骨髓瘤患者中导致深度、持久的缓解。

在这项国际性、开放标签的3期临床试验中，既往接受过2-4种方案（包括免疫调节剂、蛋白酶体抑制剂和达雷木单抗）且对最后一种方案有顽固性疾病复发和难治性多发性骨髓瘤患者，以2：1的比例随机分配患者接受ide-cel（剂量范围为150×10⁶至450×10⁶ CAR阳性T细胞）或五种标准方案之一。主要终点为无进展生存期。关键次要终点是总缓解（部分缓解或更好）和总生存期。同时进行安全性评估。

共有386例患者接受了随机分组：254例采用ide-cel，132例采用标准方案。共有66%的患者患有三级难治性疾病，95%的患者患有达雷木单抗难治性疾病。在中位随访18.6个月时，ide-cel组的中位无进展生存期为13.3个月，而标准方案组为4.4个月，疾病进展或死亡的危险比为0.49。ide-cel组71%的患者出现缓解，标准方案组有42%的患者；完全缓解率分别为39%和5%，组间差异均显著。

总体生存率的数据尚不成熟。ide-cel组93%的患者发生3级或4级不良事件，标准方案组有75%的患者发生不良事件。在接受ide-cel治疗的225例患者中，88%的患者发生细胞因子释放综合征，5%的患者发生3级或更高级别的事件，15%的患者发生研究人员确定的神经毒性作用，3%的患者发生3级或更高级别的事件。

研究结果表明，与标准方案相比，ide-cel治疗显著延长了三级暴露的复发难治性多发性骨髓瘤患者的无进展生存期，并改善了患者的缓解率，这些患者之前接受了2-4种方案。ide-cel的毒性与之前的报道一致。

附：英文原文

Title: Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma | NEJM

Author: Paula Rodriguez-Otero, M.D., Ph.D.,, Sikander Ailawadhi, M.D.,, Bertrand Arnulf, M.D., Ph.D.,, Krina Patel, M.D.,, Michele Cavo, M.D.,, Ajay K. Nooka, M.D., M.P.H.,, Salomon Manier, M.D., Ph.D.,, Natalie Callander, M.D.,, Luciano J. Costa, M.D., Ph.D.,, Ravi Vij, M.D.,, Nizar J. Bahlis, M.D.,, Philippe Moreau, M.D.,, Scott R. Solomon, M.D.,, Michel Delforge, M.D.,, Jesus Berdeja, M.D.,, Anna Truppel-Hartmann, M.D.,, Zhihong Yang, Ph.D.,, Linda Favre-Kontula, Ph.D.,, Fan Wu, Ph.D.,, Julia Piasecki, B.A.,, Mark Cook, M.B., Ch.B., Ph.D.,, and Sergio Giralt, M.D.

Issue&Volume: 2023-02-10

Abstract:

Background

Survival is poor among patients with triple-class–exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma.

Methods

In this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150×106 to 450×106 CAR-positive T cells) or one of five standard regimens. The primary end point was progression-free survival. Key secondary end points were overall response (partial response or better) and overall survival. Safety was assessed.

Results

A total of 386 patients underwent randomization: 254 to ide-cel and 132 to a standard regimen. A total of 66% of the patients had triple-class–refractory disease, and 95% had daratumumab-refractory disease. At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the ide-cel group, as compared with 4.4 months in the standard-regimen group (hazard ratio for disease progression or death, 0.49; 95% confidence interval, 0.38 to 0.65; P<0.001). A response occurred in 71% of the patients in the ide-cel group and in 42% of those in the standard-regimen group (P<0.001); a complete response occurred in 39% and 5%, respectively. Data on overall survival were immature. Adverse events of grade 3 or 4 occurred in 93% of the patients in the ide-cel group and in 75% of those in the standard-regimen group. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88%, with 5% having an event of grade 3 or higher, and investigator-identified neurotoxic effects occurred in 15%, with 3% having an event of grade 3 or higher.

Conclusions

Ide-cel therapy significantly prolonged progression-free survival and improved response as compared with standard regimens in patients with triple-class–exposed relapsed and refractory multiple myeloma who had received two to four regimens previously. The toxicity of ide-cel was consistent with previous reports.

DOI: 10.1056/NEJMoa2213614

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2213614