Souren Laura, Ihorst Gabriele, Greil Christine, Engelhardt Monika, Wäsch Ralph
Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
Comprehensive Cancer Center Freiburg (CCCF), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
Ann Hematol. 2025 Feb;104(2):1059-1067. doi: 10.1007/s00277-024-05991-7. Epub 2024 Sep 23.
Daratumumab is an effective therapy in multiple myeloma (MM). We assessed whether daratumumab retreatment may re-induce significant responses and which patients do benefit the most. We hypothesized, that there is effective synergism between daratumumab and alternating antimyeloma drug combinations during retreatment and that retreatment is safe and effective. Here, we analyzed 293 consecutive MM patients receiving daratumumab at our institution from 2016 until 2023 retrospectively, and compared responses, side effects and survival of the first daratumumab treatment line and its retreatment. We identified 22/293 (8%) patients with daratumumab retreatment. These patients showed an advanced age and ISS/R-ISS stages, and ≥ 3 lines of prior antimyeloma therapy in 91%. Of note, the median durations of the first and subsequent daratumumab treatment were similarly long. We confirmed a therapy break between daratumumab lines as advantageous. Daratumumab retreatment was effective, with responses declining only gradually from its first use to subsequent first and second retreatment with 64%, 46% and 43%, respectively. Interestingly, comparable progression free survival rates were observed with 11.5, 12 months and not reached, respectively. Consistently, adverse events per daratumumab line did not increase. Our findings suggest that well-selected daratumumab-exposed MM patients may show rewarding responses to daratumumab retreatment, the more with alternating antimyeloma combinations, initial good response and CD38-antibody-treatment pauses, thereby proving CD38-antibody-retreatment as feasible, effective and non-toxic. Confirmatory studies are required to further validate our results.
达雷妥尤单抗是治疗多发性骨髓瘤（MM）的一种有效疗法。我们评估了达雷妥尤单抗再次治疗是否可再次诱导显著反应以及哪些患者获益最大。我们假设，在再次治疗期间，达雷妥尤单抗与交替使用的抗骨髓瘤药物组合之间存在有效的协同作用，并且再次治疗是安全有效的。在此，我们回顾性分析了2016年至2023年在我们机构接受达雷妥尤单抗治疗的293例连续MM患者，并比较了首个达雷妥尤单抗治疗线及其再次治疗的反应、副作用和生存率。我们确定了22/293例（8%）接受达雷妥尤单抗再次治疗的患者。这些患者年龄较大，国际分期系统（ISS）/修订的国际分期系统（R-ISS）分期较晚，91%的患者接受过≥3线的既往抗骨髓瘤治疗。值得注意的是，首个和后续达雷妥尤单抗治疗的中位持续时间同样长。我们证实达雷妥尤单抗治疗线之间的治疗中断是有利的。达雷妥尤单抗再次治疗是有效的，反应率从首次使用到随后的首次和第二次再次治疗仅逐渐下降，分别为64%、46%和43%。有趣的是，观察到的无进展生存率分别为11.5个月、12个月和未达到，具有可比性。同样，每条达雷妥尤单抗治疗线的不良事件并未增加。我们的研究结果表明，精心挑选的接受过达雷妥尤单抗治疗的MM患者可能对达雷妥尤单抗再次治疗表现出有益的反应，尤其是联合交替使用抗骨髓瘤药物组合、初始反应良好以及CD38抗体治疗中断的患者，从而证明CD38抗体再次治疗是可行、有效且无毒的。需要进行验证性研究以进一步证实我们的结果。
