一项真实世界回顾性前瞻性分析联合来那度胺、伊沙佐米和地塞米松治疗复发/难治性多发性骨髓瘤的疗效和安全性：意大利北部经验。
A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.
机构信息
Divisione di Ematologia Ospedale Ca' Foncello di Treviso, ASL 2, Treviso, Italy.
Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCSS Ospedale Policlinico San Martino, Genova, Italy.
出版信息
Cancer Med. 2024 Apr;13(7):e7071. doi: 10.1002/cam4.7071.
INTRODUCTION
Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1.
OBJECTIVES AND METHODS
We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life.
RESULTS
At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high-risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)-exposed (including both Len-sensitive and Len-refractory pts), and 22% were Len-refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non-hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1-2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow-up of 38 m, median PFS (mPFS) was 16 m and the 1-year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len-naïve (NR), age ≥70 (20 m). In pts exposed to Len, non-refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len-refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31).
CONCLUSION
IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len-sensitive, independent of age, and cytogenetic risk.
简介
依沙佐米、来那度胺和地塞米松（IRd）在 TOURMALINE-MM1 研究中取得了复发/难治性多发性骨髓瘤（RRMM）的治疗效果后被批准使用。
目的和方法
我们对意大利北部 21 个中心的 106 例 RRMM 患者进行了回顾性前瞻性分析，旨在评估 IRd 在真实世界中的疗效和安全性。
结果
在 IRd 起始时，34%的患者年龄≥75 岁（中位数 72.5 岁），8.5%的患者 ECOG 体能状态评分≥2，54.7%可评估患者存在高危细胞遗传学异常[del17p 和/或 t(4;14)和/或 t(14;16)和/或 1g 增益/扩增]，60.2%的患者接受了≥2 线的治疗（既往线治疗，pLoT），57.5%的患者接受过来那度胺（Len）治疗（包括 Len 敏感和 Len 耐药患者），22%的患者为 Len 耐药。主要的≥3 级不良事件（AE）为血小板减少（16%）和中性粒细胞减少（12.3%）。≥3 级非血液学 AE 包括感染（9.4%）和胃肠道毒性（腹泻 5.7%，肝毒性 2.8%）、静脉血栓栓塞、皮疹和周围神经病主要为 1-2 级。总体缓解率为 56.4%（≥非常好的部分缓解，VGPR 30%）。中位随访 38 个月时，中位无进展生存期（mPFS）为 16 个月，1 年总生存率为 73%。根据亚组分析，达到≥VGPR 的患者（mPFS 21.2 个月）、从诊断到 IRd 时间≥5 年（mPFS 26.2 个月）、既往线治疗 1 线（mPFS 34.4 个月）、Len 初治（NR）、年龄≥70 岁（mPFS 20 个月）的患者，观察到了更久的 PFS。在既往任何一线治疗中对 Len 无耐药且在开始 IRd 前对 Len 敏感的患者中，mPFS 分别为 16 个月和 18 个月。Len 耐药患者的 PFS 较差（4.6 个月）。多变量分析显示，PFS 的独立预测因素包括年龄≥70 岁（HR 0.6）、从诊断到时间≥5 年（HR 0.32）、任何既往线治疗中对 Len 耐药（HR 3.33）以及治疗前即刻对 Len 耐药（HR 4.31）。
结论
IRd 可能对疾病惰性、处于早期治疗线、且之前对 Len 敏感的 RRMM 患者有效且安全，与年龄和细胞遗传学风险无关。
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