Clinical outcomes of retreatment with daratumumab-based regimens in anti-CD38 refractory multiple myeloma.
Authors: Tan Carlyn Rose Co , Rueda Colin , Shekarkhand Tala , Derkach Andriy , Korde Neha , Maclachlan Kylee , Hultcrantz Malin , Hassoun Hani , Mailankody Sham , Shah Urvi A , Rajeeve Sridevi , Lahoud Oscar Boutros , Shah Gunjan L. , Scordo Michael , Chung David J. , Landau Heather Jolie , Giralt Sergio , Usmani Saad Zafar , Lesokhin Alexander M. 
Published: June 2024

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Background: Daratumumab (Dara)-based regimens have resulted in deep responses and improved outcomes in newly diagnosed (NDMM) and relapsed/refractory multiple myeloma (RRMM). As the use of dara has increased in both settings, understanding the utility of retreating patients (pts) with dara-based therapy is important. Our prior work showed that pts treated with dara-based induction can derive benefit from dara-based retreatment. Herein, we examined outcomes of dara-based retreatment (D2) in pts with RRMM. Methods: We conducted a retrospective study of pts with RRMM who received D2 at Memorial Sloan Kettering from 1/1/2015 to 12/31/2021. Cutoff date for analysis was 1/9/2024. Pts who received ³1 cycle of dara-based therapy as the initial dara-based regimen (D1) and D2 were included. Response was assessed by IMWG response criteria. Discrete pt characteristics were summarized by frequency (%) and continuous characteristics were summarized by median (Interquartile Range, IQR). Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier method. Results: In 128 RRMM pts who received D2, median age at start of D2 was 66 (IQR 59-73); 50% male; 17% Black; ISS Stage I 45%, II 35%, III 19%; and 44% had high-risk cytogenetics (gain/amp 1q, t(4;14), t(14;16), t(14;20), del(17p)). Median prior lines of therapy (LOT) at D1 was 3 (range 2-10) and at D2 was 5 (3-14). Median time between end of D1 and start of D2 was 7.3 months (IQR 3-15.6). Of 119 pts with dara-refractory status, 100 were dara-refractory at D2. Overall response rate (ORR) was 54% for D1 and 51% for D2 for response-evaluable pts. Median duration of therapy for D2 was 4.7 months (1.8-11.3) and median time to next treatment for D2 was 8.2 months (5.8-11.4). After a median follow-up (mFU) of 56.4 months from start of D2, median PFS (mPFS) for D2 was 8.2 months (95%CI 5.3-11.2) and median OS was 43 months (35.8-60.3). Subgroup analysis based on retreatment interval of 180 days (>180 days N=74) demonstrated no significant difference in PFS between pts who received D2 ≤180 days or >180 days from D1. Median PFS from start of D2 was 8.2 months (95%CI 3.9-19.3) for ≤180-days cohort and 7.6 months (5.3-11.5) for >180-days cohort (P=0.35). When comparing outcomes of pts who received D2 as ≤4 LOTs and >4 LOTs, the mPFS for pts who received D2 as >4 LOTs was 5.4 months compared to 13.9 months for pts who received D2 as ≤4 LOT (P=0.002). Conclusions: In this retrospective study, dara retreatment yielded similar ORR compared to initial dara-based therapy in RRMM, despite a large proportion of pts being dara-refractory prior to D2. Our findings suggest that retreatment with dara in combination with other active MM agents can generate responses in pts with RRMM who are dara-refractory.[Table: see text]