Clinical efficacy of daratumumab (DARA)-based second line therapy after DARA-containing and DARA-free induction therapies in multiple myeloma: A single center experience.

Abstract

e20005 Background: DARA has been FDA approved for newly diagnosed multiple myeloma (NDMM) in combination with lenalidomide/dexamethasone (Rd), bortezomib/melphalan/dex, and bortezomib/thalidomide/dex since 2018. With the increase use of DARA combinations in NDMM, understanding the role of DARA retreatment at relapse needs to be examined in clinical practice. Herein, we describe a single institution experience of the efficacy of DARA-based retreatment as second line of therapy (LOT2) for patients (pts) who received DARA-based induction compared to DARA-free induction regimens. Methods: Thirty-three pts treated with DARA-based LOT2 at MSK from 1/2015 to 9/2021 were included in this retrospective analysis. Primary endpoint was overall response rate (ORR; ≥PR by IMWG criteria). Discrete patient characteristics were summarized by frequency (percentage) and continuous characteristics were summarized by median (IQR). Progression free survival (PFS) was evaluated by Kaplan-Meier method. Results: Two cohorts were identified based on prior DARA exposure: cohort 1 (N=6) received DARA-based induction without meeting DARA-refractory criteria and cohort 2 (N=27) had carfilzomib and Rd (KRd) induction (Table). Median follow-up was 13.8 and 14.5 months for cohorts 1 and 2, respectively. In cohort 1, 5 pts received DARA-KRd and 1 had DRd as first line therapy (LOT1). Median time between last dose of DARA in LOT1 and first dose of DARA in LOT2 was 17.5 months (IQR 12.1-19.8). ORR were 83% and 79% for cohorts 1 and 2, respectively. In cohort 1, ORR comprised of 1 sCR, 1 VGPR, and 3 PR. For cohort 2, there were 5 sCR/CR, 7 VGPR, and 9 PR. Median PFS was not reached in cohort 1 and 16.2 months in cohort 2. Conclusions: In a cohort of pts retreated with DARA after DARA-based induction, our findings suggest that DARA-exposed MM pts may derive benefit from DARA retreatment in subsequent lines of therapy similarly to pts who were DARA-naïve prior to DARA-based LOT2. Longer follow-up is needed to assess survival outcomes. In addition, larger confirmatory studies are warranted to further characterize response characteristics of DARA combinations in LOT2, especially as DARA-based therapy is increasingly used in treating NDMM. [Table: see text]