Martino Enrica Antonia, Derudas Daniele, Rossi Elena, Stefanoni Paola, Mangiacavalli Silvia, Zamagni Elena, Offidani Massimo, Furlan Anna, Quinto Angela Maria, Della Pepa Roberta, Bertuglia Giuseppe, Barbieri Emiliano, Conticello Concetta, De Magistris Claudio, Bongarzoni Velia, Cafro Anna Maria, Mele Anna, Botta Cirino, Sgherza Nicola, Mele Giuseppe, Annibali Ombretta, Rago Angela, Fontana Raffaele, Vigna Ernesto, Bruzzese Antonella, Mancuso Katia, Amendola Angela, Citro Annalisa, Cotzia Emilia, Morè Sonia, Rivolti Elena, Pettine Loredana, Galli Monica, De Stefano Valerio, Petrucci Maria Teresa, Corso Alessandro, Neri Antonino, Di Raimondo Francesco, Bolli Niccolò, Musto Pellegrino, Morabito Fortunato, Gentile Massimo
Department of Onco-hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Department of Hematology, Businco Hospital, Cagliari, Italy.
Hematol Oncol. 2025 Mar;43(2):e70042. doi: 10.1002/hon.70042.
This multicenter real-world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara-R). The majority were under 70 years old (60.8%), predominantly female (56.9%), and heavily pretreated, with 74.5% being triple-class refractory (TCR); 32.1% of the 28 patients with cytogenetic data had high-risk abnormalities. The overall response rate (ORR) was 56.9%, including 3 patients with stringent complete response (sCR), 4 with CR, and 7 with very good partial response (VGPR). Neither age, number of prior therapies, TCR status, nor time from Dara refractoriness to IsaPd initiation significantly affected response rates. Median progression-free survival (PFS) was 5.8 months, with a 12-month PFS probability of 30.6%. Baseline hemoglobin (Hb) levels were a key predictor of PFS: patients with Hb < 11.8 g/L had a 3.5-fold increased risk of progression, with a median PFS of 4.6 months compared to 22 months in those with higher Hb. Median overall survival (OS) was 21.0 months, with a 12-month OS probability of 63.4%. Lower Hb levels (< 11 g/L) were associated with a tenfold increased risk of mortality. Among the 28 patients who underwent FISH analysis, while no significant difference in mortality risk was observed, those with high-risk cytogenetic abnormalities exhibited a nearly tenfold increased risk of disease progression. These results suggest that IsaPd offers a meaningful option for Dara-R patients, with Hb levels serving as a critical predictor of both PFS and OS. However, PFS remains modest, underscoring the need for novel combination therapies.
这项多中心真实世界分析评估了isatuximab、泊马度胺和地塞米松（IsaPd）对51例对达雷妥尤单抗难治（Dara-R）的多发性骨髓瘤（MM）患者的疗效。大多数患者年龄在70岁以下（60.8%），以女性为主（56.9%），且接受过大量预处理，74.5%为三重耐药（TCR）；在28例有细胞遗传学数据的患者中，32.1%有高危异常。总缓解率（ORR）为56.9%，包括3例严格完全缓解（sCR）、4例完全缓解（CR）和7例非常好的部分缓解（VGPR）。年龄、既往治疗次数、TCR状态以及从达雷妥尤单抗难治到开始使用IsaPd的时间均未显著影响缓解率。无进展生存期（PFS）中位数为5.8个月，12个月PFS概率为30.6%。基线血红蛋白（Hb）水平是PFS的关键预测指标：Hb<11.8g/L的患者进展风险增加3.5倍，PFS中位数为4.6个月，而Hb较高者为22个月。总生存期（OS）中位数为21.0个月，12个月OS概率为63.4%。较低的Hb水平（<11g/L）与死亡风险增加10倍相关。在28例接受荧光原位杂交（FISH）分析的患者中，虽然未观察到死亡风险有显著差异，但有高危细胞遗传学异常的患者疾病进展风险增加近10倍。这些结果表明，IsaPd为Dara-R患者提供了一个有意义的选择，Hb水平是PFS和OS的关键预测指标。然而，PFS仍然有限，凸显了对新型联合疗法的需求。
