Daratumumab-Based Second Line Therapy Improves Outcomes After VRD Induction, Upfront Autologous Transplant, and Lenalidomide Maintenance

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2026-05-01 Epub Date: 2026-03-05 DOI:10.1016/j.clml.2026.02.014

Oren Pasvolsky , Curtis Marcoux , Denái R. Milton , Mark R. Tanner , Qaiser Bashir , Samer Srour , Neeraj Saini , Paul Lin , Umer R. Siddiqui , Hina N. Khan , Asad A. Haider , Jeremy Ramdial , Yago Nieto , Guilin Tang , Kiran Lakhani , Yosra Aljawai , Partow Kebriaei , Hans C. Lee , Krina K. Patel , Sheeba K. Thomas , Muzaffar H. Qazilbash

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Abstract

Background

For eligible patients with newly diagnosed multiple myeloma (MM), induction with VRD used to be the standard of care, followed by autologous stem cell transplantation (autoHCT) and lenalidomide maintenance. Most patients relapse and require second-line (2L) therapy.

Patients and Methods

We conducted a retrospective, single-center study of MM patients who received VRD induction, autoHCT between 2005-2021, and lenalidomide maintenance before relapse.

Results

A total number of 146 patients were included, with a median age of 60 years (range, 32-80), and 39 (27%) patients had high-risk cytogenetics. Following first progression, 31%received an immunomodulatory drug (IMiD) + proteasome inhibitor (PI)-containing triplet as 2L therapy, 21% received an IMiD/PI-containing doublet, and 24% received a daratumumab (Dara)-based 2L therapy. Patients receiving Dara-based regimens had higher rates of ≥VGPR (63%) compared to those receiving other regimens (IMiD + PI triplet: 35%, IMiD/PI doublet: 34%) (P = .026). After a median follow-up of 35.8 months from 2L therapy, median PFS2 with Dara-based regimens was 59.9 months, versus 12.3 months and 11.5 months for doublets and triplets, respectively (P = .007). Median overall survival (OS) for the entire cohort was 52.6 months. In multivariable analysis, Dara-based therapy was associated with improved PFS2 (HR 0.35, P < .001), while clinical progression (vs. biochemical) predicted worse PFS2 (HR 1.58, P = .026). Progression ≥ 12 months post-autoHCT was associated with improved OS (HR 0.23, P < .001); busulfan−melphalan conditioning (HR 4.06, P < .001) and clinical progression (HR 1.99, P = .006) were associated with inferior OS.

Conclusion

Dara-based 2L regimens were associated with superior PFS2 approaching almost 5 years.

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以达拉图单抗为基础的二线治疗改善VRD诱导、前期自体移植和来那度胺维持后的预后。

背景：对于符合条件的新诊断多发性骨髓瘤（MM）患者，VRD诱导曾经是标准的治疗方法，随后是自体干细胞移植（autoHCT）和来那度胺维持。大多数患者复发，需要二线（2L）治疗。患者和方法：我们对2005-2021年间接受VRD诱导、自体hct和复发前来那度胺维持的MM患者进行了一项回顾性、单中心研究。结果：共纳入146例患者，中位年龄为60岁（范围32-80岁），39例（27%）患者具有高危细胞遗传学。在首次进展后，31%的患者接受了免疫调节药物(IMiD) +含蛋白酶体抑制剂（PI）的三重药物作为2L治疗，21%的患者接受了含IMiD/PI的双重药物治疗，24%的患者接受了基于达拉单抗（Dara）的2L治疗。与接受其他方案（IMiD + PI三重态：35%，IMiD/PI三重态：34%）的患者相比，接受基于dara方案的患者的VGPR≥率（63%）更高（P = 0.026）。2L治疗的中位随访时间为35.8个月，基于dara的方案的中位PFS2为59.9个月，而双胞胎和三胞胎的中位PFS2分别为12.3个月和11.5个月（P = .007）。整个队列的中位总生存期（OS）为52.6个月。在多变量分析中，基于dara的治疗与PFS2改善相关（HR 0.35, P < 0.001），而临床进展（vs.生化）预测PFS2恶化（HR 1.58, P = 0.026）。autohct后进展≥12个月与OS改善相关（HR 0.23, P < 0.001）；布苏芬-美法兰调节（HR 4.06, P < 0.001）和临床进展（HR 1.99, P = 0.006）与不良OS相关。结论：基于dara的2L方案与接近5年的优越PFS2相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Lymphoma, Myeloma & Leukemia ONCOLOGY-HEMATOLOGY

CiteScore

2.70

自引率

3.70%

发文量

1606

审稿时长

26 days

期刊介绍： Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed monthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma & Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.