法国里尔大学中心医院Thierry Facon团队研究了艾萨妥昔单抗、硼替佐米、来那度胺和地塞米松治疗多发性骨髓瘤的疗效与安全性。该研究于2024年6月3日发表在《新英格兰医学杂志》上。

硼替佐米、来那度胺和地塞米松（VRd）是新诊断的多发性骨髓瘤患者的首选一线治疗方案。在VRd方案中加入抗CD38单克隆抗体艾萨妥昔单抗是否会降低不符合移植条件患者的疾病进展或死亡风险尚不清楚。

在一项国际开放标签3期试验中，研究组以3:2的比例随机分配18至80岁的新诊断多发性骨髓瘤患者，这些患者不适合接受移植，接受艾萨妥昔单抗加VRd或单独接受VRd。主要疗效终点是无进展生存期。关键次要终点包括完全缓解或好转，以及完全缓解和最小残留疾病（MRD）阴性状态。

共有446名患者接受了随机分组。在59.7个月的中位随访中，与VRd组的45.2%相比，艾萨妥昔单抗+VRd组在60个月时的估计无进展生存率为63.2%（疾病进展或死亡的风险比为0.60；98.5%置信区间为0.41至0.88；P<0.001）。艾萨妥昔单抗VRd组完全缓解或好转的患者比例显著高于VRd组（74.7%对64.1%，P=0.01），MRD阴性和完全缓解的患者比例也显著高于VRd组（55.5%对40.9%，P=0.003）。艾萨妥昔单抗+VRd方案未观察到新的安全性信号。两组治疗期间严重不良事件的发生率和导致停药的不良事件发生率相似。

研究结果表明，艾萨妥昔单抗联合VRd作为18至80岁新诊断的不符合移植条件的，多发性骨髓瘤患者的初始治疗比VRd更有效。

附：英文原文

Title: Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

Author: Thierry Facon, Meletios-Athanasios Dimopoulos, Xavier P. Leleu, Meral Beksac, Ludek Pour, Roman Hájek, Zhuogang Liu, Jiri Minarik, Philippe Moreau, Joanna Romejko-Jarosinska, Ivan Spicka, Vladimir I. Vorobyev, Britta Besemer, Tadao Ishida, Wojciech Janowski, Sevgi Kalayoglu-Besisik, Gurdeep Parmar, Pawel Robak, Elena Zamagni, Hartmut Goldschmidt, Thomas G. Martin, Salomon Manier, Mohamad Mohty, Corina Oprea, Marie-France Brégeault, Sandrine Macé, Christelle Berthou, David Bregman, Zandra Klippel, Robert Z. Orlowski

Issue&Volume: 2024-06-03

Abstract:

BACKGROUND

Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

METHODS

In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)–negative status in patients with a complete response.

RESULTS

A total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; P<0.001). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P=0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P=0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups.

CONCLUSIONS

Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation.

DOI: NJ202406030000017

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2400712