Ailawadhi Sikander, Arnulf Bertrand, Patel Krina, Cavo Michele, Nooka Ajay K, Manier Salomon, Callander Natalie, Costa Luciano J, Vij Ravi, Bahlis Nizar J, Moreau Philippe, Solomon Scott, Abrahamsen Ingerid Weum, Baz Rachid, Broijl Annemiek, Chen Christine, Jagannath Sundar, Raje Noopur, Scheid Christof, Delforge Michel, Benjamin Reuben, Pabst Thomas, Iida Shinsuke, Berdeja Jesús, Giralt Sergio, Truppel-Hartmann Anna, Chen Yanping, Zhong Xiaobo, Wu Fan, Piasecki Julia, Eliason Laurie, Dhanda Devender, Felten Jasper, Caia Andrea, Cook Mark, Popa McKiver Mihaela, Rodríguez-Otero Paula
Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL.
Immuno-Hématologie, Hôpital Saint-Louis, l'Assistance publique-Hôpitaux de Paris, Université Paris Cite, Paris, France.
Blood. 2024 Dec 5;144(23):2389-2401. doi: 10.1182/blood.2024024582.
Outcomes are poor in triple-class-exposed (TCE) relapsed and refractory multiple myeloma (R/RMM). In the phase 3 KarMMa-3 trial, patients with TCE R/RMM and 2 to 4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary end point; 13.3 vs 4.4 months; P < .0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median was 41.4 (95% CI, 30.9 to not reached [NR]) vs 37.9 (95% CI, 23.4 to NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI, 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE R/RMM. This trial was registered at www.ClinicalTrials.gov as #NCT03651128.
在接受三重疗法暴露（TCE）的复发难治性多发性骨髓瘤（R/RMM）患者中，预后较差。在3期KarMMa-3试验中，接受过2至4种先前治疗方案的TCE R/RMM患者按2:1随机分组，分别接受idecabtagene vicleucel（ide-cel）或标准方案（SRs）治疗。一项中期分析（IA）显示，与SRs相比，ide-cel的中位无进展生存期（PFS；主要终点；13.3个月对4.4个月；P <.0001）显著更长，总缓解率（ORR）更高。在最终PFS分析时（中位随访30.9个月），与SRs相比，ide-cel进一步改善了中位PFS（13.8个月对4.4个月；风险比[HR]，0.49；95%置信区间[CI]，0.38-0.63）。无论先前治疗线数多少，与SRs相比，ide-cel均显示出PFS获益，在前2线治疗后获益最大（分别为16.2个月对4.8个月）。与SRs相比，ide-cel维持了ORR获益（71%对42%；完全缓解率，44%对5%）。以患者为中心的设计允许疾病进展时从SRs组（56%）交叉至ide-cel组，这混淆了总生存期（OS）的解读。在IA阶段的OS分析中，ide-cel组和SRs组的中位OS分别为41.4（95%CI，30.9至未达到[NR]）个月和37.9（95%CI，23.4至NR）个月（HR，1.01；95%CI，0.73-1.40）；两组的中位OS均长于历史数据（9-22个月）。两项针对交叉情况进行调整的预设分析显示OS有利于ide-cel组。该试验强调了个体化桥接治疗的重要性，以确保在ide-cel制备过程中实现充分的疾病控制。与SRs相比，ide-cel改善了患者报告的结局。未报告新的安全信号。这些结果表明ide-cel在一线及TCE R/RMM中持续具有良好的获益风险比。该试验已在www.ClinicalTrials.gov上注册，编号为#NCT03651128。
