Costa Luciano J, Gay Francesca, Landgren Ola, Mateos María-Victoria, Moreau Philippe, Touzeau Cyrille, Ertel Franziska, McFadden Ian, Najdi Rani, Weisel Katja
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham Hospital, 1802 6Th Avenue South, Birmingham, AL, 35294, USA.
AOU Città Della Salute E Della Scienza Di Torino, University of Torino, Turin, Italy.
Ann Hematol. 2025 Mar;104(3):1329-1351. doi: 10.1007/s00277-024-06143-7. Epub 2025 Jan 8.
Although survival rates for patients with newly diagnosed multiple myeloma (NDMM) have improved over recent decades, multiple myeloma (MM) remains without a cure for most. There is increasing consensus that achievement of deep remissions, especially minimal residual disease negativity (MRD -), in frontline treatment is crucial and translates into improved survival. The standard of care (SOC) for NDMM consists at minimum of a triplet regimen of therapies, with or without an autologous stem cell transplant, or a doublet regimen for certain ineligible, particularly frail patients who may have specific limitations. Recently, anti-CD38 monoclonal antibodies (mAbs), such as daratumumab (Dara) or isatuximab (Isa), have been integrated into frontline SOC regimens. Seeking to further deepen and prolong responses, several clinical trials have commenced investigating the addition of anti-CD38 mAbs to carfilzomib, lenalidomide, and dexamethasone (KRd). These quadruplet regimens (Isa/Dara-KRd) are being evaluated in the context of evolving treatment considerations for the heterogeneous population of patients with NDMM. In clinical trials, the addition of Isa/Dara to KRd achieved high rates of deep responses and MRD - . Favorable outcomes were observed in patients with NDMM independent of age, transplant eligibility, and cytogenetic risk, while these treatments did not result in unexpected or emergent safety risks. The efficacy observed with intensified, yet well-tolerated therapy may offer further development of risk- and response-adapted therapy for individualized patient needs. This review summarizes the clinical outcomes of quadruplet-based therapy with Isa/Dara-KRd in NDMM.
尽管近几十年来新诊断的多发性骨髓瘤（NDMM）患者的生存率有所提高，但多发性骨髓瘤（MM）对大多数患者来说仍然无法治愈。越来越多的共识认为，在一线治疗中实现深度缓解，尤其是微小残留病阴性（MRD-）至关重要，并且能转化为生存率的提高。NDMM的标准治疗（SOC）至少包括三联疗法，联合或不联合自体干细胞移植，或者对于某些不符合条件、特别是可能有特定限制的体弱患者采用双联疗法。最近，抗CD38单克隆抗体（mAb），如达雷妥尤单抗（Dara）或isatuximab（Isa），已被纳入一线SOC方案。为了进一步加深和延长缓解期，几项临床试验已开始研究在卡非佐米、来那度胺和地塞米松（KRd）中加入抗CD38 mAb。这些四联方案（Isa/Dara-KRd）正在针对NDMM异质性患者群体不断演变的治疗考虑因素进行评估。在临床试验中，在KRd中加入Isa/Dara可实现高深度缓解率和MRD-。在NDMM患者中观察到了良好的结果，与年龄、移植资格和细胞遗传学风险无关，而这些治疗并未导致意外或突发的安全风险。强化但耐受性良好的治疗所观察到的疗效可能为根据个体患者需求进行风险和反应适应性治疗提供进一步发展方向。本综述总结了NDMM中基于Isa/Dara-KRd的四联疗法的临床结果。
