Quadruplet regimens comprising an anti-CD38 antibody, proteasome inhibitor, immunomodulatory agent and a glucocorticoid have become the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). A quadruplet regimen has also been approved for transplant-ineligible patients, although one built on a triplet containing melphalan instead of an immunomodulatory agent. Now, data from the phase III IMROZ and BENEFIT trials indicate that integration of the anti-CD38 antibody isatuximab (Isa) with the standard, first-line bortezomib (V), lenalidomide (R) and dexamethasone (d) triplet results in more durable responses in this population.

In IMROZ, 446 transplant-eligible patients ≤80 years of age with NDMM were randomly assigned (3:2) to receive 4 cycles of Isa-VRd or VRd followed by continuous Isa-Rd or Rd, respectively. The primary end point was progression-free survival (PFS). At a median follow-up of 59.7 months, 60-month PFS was 63.2% with Isa-VRd versus 45.2% with VRd (HR 0.60, 98.5% CI 0.41–0.88; P < 0.001). Significantly more patients receiving Isa-VRd had a complete response or better (74.7% versus 64.1%; P = 0.01) and were rendered minimal residual disease (MRD)-negative at 10⁻⁵ sensitivity on next-generation sequencing (55.5% versus 40.9%; P = 0.003). Although the data remain immature, a trend towards improved overall survival was also observed (72.3% versus 66.3%; HR 0.78, 99.97% CI 0.41–1.48). The two regimens were associated with similar safety profiles, rates of discontinuation owing to adverse events and quality-of-life scores, albeit with a notably higher incidence of grade ≥3 neutropenia, leukopenia and infections, second primary cancers, and fatal adverse events (mostly infections) in patients receiving Isa-VRd.

由抗 CD38 抗体、蛋白酶体抑制剂、免疫调节剂和糖皮质激素组成的四联方案已成为符合移植条件的新诊断多发性骨髓瘤 （NDMM） 患者的标准治疗。四联方案也被批准用于不适合移植的患者，尽管一种方案建立在含有美法仑而不是免疫调节剂的三联体之上。现在，来自 III 期 IMROZ 和 BENEFIT 试验的数据表明，抗 CD38 抗体 isatuximab （Isa） 与标准一线硼替佐米 （V）、来那度胺 （R） 和地塞米松 （d） 三联体的整合可在该人群中产生更持久的反应。

在 IMROZ 中，446 名符合移植条件的患者 ≤80 岁的 NDMM 患者被随机分配 （3：2） 接受 4 个周期的 Isa-VRd 或 VRd，然后分别接受连续 Isa-Rd 或 Rd。主要终点是无进展生存期 （PFS）。中位随访 59.7 个月时，Isa-VRd 组的 60 个月 PFS 为 63.2%，VRd 组为 45.2%（HR 0.60,98.5% CI 0.41-0.88;P < 0.001）。接受 Isa-VRd 的患者完全缓解或更好（74.7% 对 64.1%;P = 0.01），并且在下一代测序中以 ^10-5 的敏感性呈现微小残留病 （MRD） 阴性 （55.5% 对 40.9%;P = 0.003）。尽管数据仍不成熟，但也观察到总生存期有提高的趋势 （72.3% 对 66.3%;HR 0.78,99.97% CI 0.41-1.48）。这两种方案具有相似的安全性、因不良事件而停药的比率和生活质量评分，尽管接受 Isa-VRd 的患者 ≥3 级中性粒细胞减少、白细胞减少和感染、第二原发癌和致命不良事件（主要是感染）的发生率明显更高。