Isatuximab Subcutaneous by On-Body Delivery System vs Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase 3 IRAKLIA Study.

IF 42.1 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2025-06-03 DOI:10.1200/JCO-25-00744

Sikander Ailawadhi, Ivan Špička, Andrew Spencer, Jin Lu, Albert Oriol, Silvia Ling, Fredrik Schjesvold, Alejandro Berkovits, Marek Hus, Chunrui Li, Meletios-Athanasios Dimopoulos, Péter Rajnics, Sevgi Kalayoğlu Beşışık, Vania Hungria, Maria Del Rosario Custidiano, Gurdeep Parmar, Xavier Leleu, Fei Li, Claudio Cerchione, Cesar Gomez, Tadao Ishida, Maria Victoria Mateos, Tondre T Buck, Richard LeBlanc, Jiří Minařík, Hartmut Goldschmidt, Rick Zhang, Dorothée Sémiond, Florence Suzan, Maya Stefanova-Urena, Victorine Koch, Philippe Moreau

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引用次数: 0

Abstract

Purpose: To report results of the multicenter, open-label IRAKLIA trial (NCT05405166) of isatuximab subcutaneous (SC) versus intravenous (IV), plus pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma (MM), the first Phase 3 MM trial using an on-body delivery system (OBDS).

Methods: Patients with ≥1 prior line of therapy were randomized 1:1 to isatuximab OBDS (1400 mg) or IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks, plus pomalidomide (4 mg/day, Day [D]1-21) and dexamethasone (40 mg weekly [age ≥75: 20 mg]) and treated until progression, unacceptable toxicity, or patient request. Co-primary endpoints were overall response rate (ORR; non-inferiority margin, 0.839) and isatuximab C_trough (C6D1 predose; non-inferiority margin, 0.8). Non-inferiority of OBDS versus IV was demonstrated if both co-primary endpoints achieved non-inferiority.

Results: IRAKLIA randomized 531 patients (OBDS, n=263; IV, n=268). After 12 months median follow-up, ORR was 71.1% (OBDS) and 70.5% (IV; relative risk [95% CI]=1.008 [0.903-1.126]; lower CI exceeded non-inferiority margin). Mean (SD) C6D1 C_trough was 499 (259) μg/mL (OBDS) and 340 (169) μg/mL (IV). C_trough geometric mean ratio (90% CI) was 1.532 (1.316-1.784); lower CI exceeded non-inferiority margin. Grade ≥3 treatment-emergent adverse event incidences were 81.7% (OBDS) and 76.1% (IV); infusion reaction incidences were 1.5% and 25.0%. Injection site reactions occurred in 0.4% of OBDS injections (all grade 1-2); 99.9% of injections completed without interruption.

Conclusion: IRAKLIA demonstrated efficacy and pharmacokinetic non-inferiority between isatuximab OBDS and IV. No unexpected safety signal was observed, with excellent local tolerability of isatuximab OBDS. Efficacy and safety were comparable to isatuximab IV in ICARIA-MM, except the lower OBDS infusion reaction rate. These results support potential use of the OBDS, designed to improve practice efficiency.

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依沙妥昔单抗皮下给药与依沙妥昔单抗静脉注射加泊马度胺和地塞米松治疗复发/难治性多发性骨髓瘤：3期IRAKLIA研究

目的：报告多中心，开放标签IRAKLIA试验（NCT05405166）的结果，isatuximab皮下（SC）与静脉（IV），加泊马度胺和地塞米松，治疗复发/难治性多发性骨髓瘤（MM），第一个3期MM试验使用体内给药系统（OBDS）。方法：既往治疗≥1条线的患者在第(C)周期1中以1:1的比例随机分配到每周一次的isatuximab OBDS （1400mg）或静脉注射（10mg /kg），然后每2周一次，加用泊马度胺（4mg /天，第[D]1-21天）和地塞米松（40mg /周[年龄≥75:20mg]）治疗，直到进展、不可接受的毒性或患者要求。共同主要终点是总缓解率（ORR）；非劣效性裕度，0.839)和isatuximab C6D1；非劣效性裕度为0.8)。如果两个共同主要终点均达到非劣效性，则证明OBDS与IV的非劣效性。结果：IRAKLIA随机抽取531例患者(OBDS, n=263；第四,n = 268)。中位随访12个月后，ORR为71.1% （OBDS）和70.5% (IV；相对危险度[95% CI]=1.008 [0.903-1.126]；较低CI超过非劣效边际)。平均（SD） C6D1 Ctrough为499 (259)μg/mL （OBDS）和340 (169)μg/mL （IV）。穿透几何平均比（90% CI）为1.532 (1.316 ~ 1.784)；较低CI超过非劣效性界限。≥3级治疗后出现的不良事件发生率分别为81.7% （OBDS）和76.1% (IV)；输液反应发生率分别为1.5%和25.0%。0.4%的OBDS注射发生了注射部位反应（均为1-2级）；99.9%的注射不间断地完成。结论：IRAKLIA在依沙妥昔单抗OBDS和IV之间表现出疗效和药代动力学的非劣效性，未观察到意外的安全性信号，依沙妥昔单抗OBDS具有良好的局部耐受性。ICARIA-MM的疗效和安全性与isatuximab IV相当，但OBDS输液反应率较低。这些结果支持OBDS的潜在应用，旨在提高实践效率。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.