Sgherza Nicola, Battisti Olga, Curci Paola, Conticello Concetta, Palmieri Salvatore, Derudas Daniele, Germano Candida, Martino Enrica Antonia, Mele Giuseppe, Pepa Roberta Della, Fazio Francesca, Mele Anna, Rossini Bernardo, Palazzo Giulia, Roccotelli Daniela, Rasola Simona, Petrucci Maria Teresa, Pastore Domenico, Tarantini Giuseppe, Pane Fabrizio, Gentile Massimo, Di Raimondo Francesco, Resta Emanuela, Musto Pellegrino
Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, 70124 Bari, Italy.
Division of Hematology and Stem Cell Transplantation, Policlinico "G. Rodolico-San Marco", 95123 Catania, Italy.
Pharmaceuticals (Basel). 2025 Apr 19;18(4):595. doi: 10.3390/ph18040595.
: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1-3 prior treatments. : Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. : After a median follow-up time of 12.9 months (range, 1-77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. : These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.
在随机3期IKEMA试验中，三联方案isatuximab、卡非佐米和地塞米松（IsaKd）在1-3线前期治疗后的复发/难治性多发性骨髓瘤患者中显示出优于单独使用卡非佐米和地塞米松的临床获益。我们的真实世界AENEID研究旨在评估IsaKd在一线来那度胺治疗后复发患者中的疗效和安全性，IKEMA试验中这类患者代表性不足。具体而言，在本多中心分析中，我们纳入了82例患者，这些患者在2022年4月至2024年9月期间且在临床试验之外，在诱导治疗、自体干细胞移植（ASCT）和来那度胺维持治疗后的首次复发时接受了至少1个周期的IsaKd作为二线治疗。中位随访时间为12.9个月（范围1-77个月），总缓解率、至少非常好的部分缓解率和中位无进展生存期分别为79.3%、56.1%和24.4个月。与IKEMA研究相比，该表现略低可能归因于我们所有患者在维持治疗期间出现的来那度胺难治性（len-R）对预后的不良影响，以及我们队列中外髓疾病患者比例较高，这在多变量分析中被确定为唯一显著影响无进展生存期的因素。与关键试验一样，中位总生存期未达到，而1年生存概率为85.1%。关于安全性，我们的发现与IKEMA试验一致，未报告新的安全信号。这些真实世界数据支持将IsaKd作为一线治疗（包括ASCT和来那度胺维持治疗）后复发的len-R MM患者的有价值选择。
