Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Pharmacy, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Br J Haematol. 2024 Apr;204(4):1300-1306. doi: 10.1111/bjh.19303. Epub 2024 Jan 30.
The combination of anti-CD38 monoclonal antibodies to a proteasome inhibitor, an immunomodulatory agent and dexamethasone (quadruplet-QUAD) in sequence with autologous stem cell transplantation (ASCT) leads to deep and durable responses in newly diagnosed multiple myeloma (NDMM). Disease progression in the first year post-QUADs is uncommon. We analysed 274 consecutive NDMM patients treated with QUADs + ASCT. After a median follow-up of 21.3 months, 20 patients had disease progression <18 months and 21 had progression ≥18 months after the onset of a QUAD regimen. All patients received subsequent anti-MM therapy, and 38 were evaluated for response. Nine (22.0%) received T-cell redirecting therapy as the next treatment, and 21 (51.2%) at some point in the treatment course. Response to next therapy was 26.3% for patients with progression <18 months and 52.6% for those with progression ≥18 months after the onset of a QUAD regimen. Median PFS on the next therapy was 2.5 months (95% CI 1.5-3.4) for those with progression <18 months and 7.0 months (95% CI 3.6-10.5) for those with progression ≥18 months. Efforts should focus on the early deployment of therapies with new mechanism of action for patients experiencing treatment failure after QUADs.
抗 CD38 单克隆抗体与蛋白酶体抑制剂、免疫调节剂和地塞米松（四联剂 QUAD）联合序贯自体干细胞移植（ASCT）可在新诊断多发性骨髓瘤（NDMM）患者中实现深度和持久的缓解。QUAD 治疗后 1 年内疾病进展并不常见。我们分析了 274 例接受 QUADs+ASCT 治疗的连续 NDMM 患者。中位随访 21.3 个月后，20 例患者在 QUAD 方案开始后 <18 个月发生疾病进展，21 例患者在 QUAD 方案开始后 ≥18 个月发生疾病进展。所有患者均接受了后续抗 MM 治疗，其中 38 例患者的疗效可评估。9 例（22.0%）患者接受了 T 细胞重定向治疗作为下一次治疗，21 例（51.2%）患者在治疗过程中的某个时间点接受了该治疗。QUAD 方案开始后 <18 个月发生疾病进展的患者中，下一治疗方案的缓解率为 26.3%，而 QUAD 方案开始后 ≥18 个月发生疾病进展的患者中，缓解率为 52.6%。QUAD 方案开始后 <18 个月发生疾病进展的患者下一治疗方案的中位 PFS 为 2.5 个月（95%CI 1.5-3.4），而 QUAD 方案开始后 ≥18 个月发生疾病进展的患者下一治疗方案的中位 PFS 为 7.0 个月（95%CI 3.6-10.5）。对于 QUAD 治疗失败的患者，应重点尽早使用具有新作用机制的疗法。
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