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. 2025 Feb;104(2):1059-1067.
doi: 10.1007/s00277-024-05991-7. Epub 2024 Sep 23.

Response to daratumumab-retreatment in patients with multiple myeloma

Laura Souren  1   2 , Gabriele Ihorst  2   3 , Christine Greil  1   2 , Monika Engelhardt  1   2 , Ralph Wäsch  4   5
Affiliations

Response to daratumumab-retreatment in patients with multiple myeloma

Laura Souren et al. Ann Hematol. 2025 Feb.

Abstract

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.

Keywords: CD38-antibody; Multiple myeloma; Retreatment.

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Conflict of interest statement

Declarations. Ethical approval: The study is registered at Freiburg Register of Clinical Trials under protocol FRKS004511 and was approved by the Ethics Committee of the University of Freiburg (EV 23-1110_1-S1). It was performed according to the guidelines of the Declaration of Helsinki and Good Clinical Practice. Informed consent: All patients gave their written informed consent for institutionally initiated research studies in accordance with the institutional review board guidelines. Competing interests: RW consulted for Amgen, BMS/Celgene, Janssen, Novartis, Kite/Gilead, Pfizer, Sanofi and Takeda, he received research funding from Janssen and Sanofi, and travel support from Janssen, Kite/Gilead, Pfizer and BMS. The other authors declare no competing financial interest related to this study.

Figures

Fig. 1
Fig. 1
Lengths of daratumumab lines and treatment breaks. D1 = first daratumumab treatment, D2 = first daratumumab retreatment, D3 = second daratumumab retreatment
Fig. 2
Fig. 2
Best responses to daratumumab treatment in respective daratumumab lines. Abbreviations: ORR: overall response rate, sCR: stringent complete remission, CR: complete remission, vgPR: very good partial remission, PR: partial remission, MR: minor response, SD: stable disease, PD: progressive disease, ORR: overall response rate, D1 = first daratumumab treatment, D2 = first daratumumab retreatment, D3 = second daratumumab retreatment
Fig. 3
Fig. 3
Direct comparison of all daratumumab lines, sorted according to the length of the first daratumumab treatment: (A) first daratumumab treatment (D1): response in 14 patients (67%), (B) first daratumumab retreatment (D2): response in 10 patients (46%) and second daratumumab retreatment (D3): response in 3 patients (43%) (response = MR or better). Abbreviations: SD: stable disease, PD: progressive disease, MR: minor response, PR: partial remission, vgPR: very good partial remission, sCR: stringent complete remission
Fig. 4
Fig. 4
PFS of all daratumumab treatment-lines. Abbreviations: dara: daratumumab, D1 = first daratumumab treatment, D2 = first daratumumab retreatment, D3 = second daratumumab retreatment
See this image and copyright information in PMC

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