P-368: Stem Cell (SC) Yield and Transplant with Daratumumab ± Bortezomib, Lenalidomide and Dexamethasone in Transplant-eligible Newly Diagnosed Multiple Myeloma Patients in the Phase 3 PERSEUS Study

Introduction: In the primary analysis of the phase 3 PERSEUS study (NCT03710603), subcutaneous daratumumab (DARA) + VRd (D-VRd) induction/consolidation (ind/consol) and D-R maintenance (maint) improved progression-free survival and increased rates of deep and durable responses, such as minimal residual disease negativity, versus VRd ind/consol and R maint in TE pts with NDMM. Here, we report stem cell (SC) yield and ASCT results for pts with TE NDMM receiving D-VRd versus VRd ind prior to HDT/ASCT in PERSEUS.

Methods: TE NDMM pts (aged 18-70 yrs) were randomized 1:1 to receive up to six 28-day cycles (4 pre-ASCT ind; 2 post-ASCT consol) of VRd ± DARA, given weekly in Cycles 1-2 and every 2 wks in Cycles 3-6. Within 6 wks after completion of ind therapy (Cycle 4) pts underwent SC mobilization per local standard of care. The use of plerixafor (per institutional practice) in addition to standard agents such as cyclophosphamide/GCSF was recommended to ensure adequate mobilization. If impacted by COVID-19 site closures, SCs were collected after Cycle 4 and transplanted immediately after completion of Cycle 6. Melphalan was given as HDT prior to ASCT.

Results: Of the 698 treated pts (D-VRd, n=351; VRd, n=347), 335 pts in the D-VRd group and 317 pts in the VRd group completed mobilization. Among pts who completed mobilization, plerixafor use was 40.0% with D-VRd and 22.7% with VRd. Median time from last ind dose to first mobilization agent was 22 days. Median number of CD34⁺ cells collected was lower with D-VRd vs VRd (5.52×10⁶/kg vs 7.44×10⁶/kg, respectively). Nevertheless, the percent of pts who underwent ASCT was similar between D-VRd and VRd groups (315/351 [89.7%] and 302/347 [87.0%], respectively). The median number of CD34⁺ cells transplanted was 3.25×10⁶/kg and 3.98×10⁶/kg, respectively. Hematopoietic reconstitution rates were high in both D-VRd (314/315 [99.7%] pts) and VRd (300/302 [99.3%] pts) groups. A median (range) of 13 (1-67) and 13 (1-38) days was needed to achieve sustained ANC of ≥0.5×10⁹/L with D-VRd and VRd, respectively; 14 (1-94) and 12 (1-137) days were needed to achieve a platelet count of ≥20×10⁹/L without transfusion. Median (range) time to engraftment post-ASCT was similar between D-VRd and VRd groups (14 [1-94] and 14 [1-137] days, respectively). A total of 58 pts (29 pts/group) underwent ASCT after completion of Cycle 6 with 100% hematopoietic reconstitution and similar median (range) time to engraftment (D-VRd, 14 [1-67] days; VRd, 14 [12-137] days) in both groups.

Conclusions: Despite D-VRd ind therapy resulting in a lower SC yield compared to VRd alone, SC mobilization and collection remained feasible with D-VRd ind. Overall, successful transplantation was achieved in pts with TE NDMM when combining DARA with VRd ind and when performed after Cycle 6.