P-216: Daratumumab, Carfilzomib, Lenalidomide, & Dexamethasone for relapsed/refractory Myeloma with salvage autologous hematopoietic cell transplant: interim analysis of the multicenter 2nd chance protocol

Background Despite major advances in multiple myeloma (MM) therapy, most patients relapse after primary treatment. We present the interim analysis of a phase II multicenter trial evaluating the efficacy of daratumumab, carfilzomib (27 mg/m2 twice weekly), lenalidomide, & dexamethasone (Dara-KRD) with high-dose melphalan and autologous hematopoietic cell transplantation (AHCT) in patients after 1-3 prior lines to induce a complete response and provide patients a 2nd chance at long term disease control. Methods Patients received 4 cycles of Dara-KRD followed by AHCT and 4 additional cycles of Dara-KRD followed by maintenance at investigator discretion with a primary endpoint of best overall response by the end of cycle 8. Using a Simon’s two-stage optimal design, 7/22 patients need to achieve a CR to continue. Patient reported outcomes were monitored monthly using the MDASI-MM and NCI PRO-CTCAE. Data cutoff was 7/15/21. Results Between 7/2018 and 7/2020, 23 patients enrolled with 22 evaluable for interim analysis (one did not complete one cycle of treatment and was replaced). Patients had a median age of 65 (range 29-73), with 68% male, 64% white, and 18% black. Time from initial MM diagnosis to enrollment was a median of 4.4 years (range 0.4 -10.6). At initial diagnosis, 36% of patients had ISS stage I disease and 31% had unknown ISS staging. High risk cytogenetics were seen in 36%, with 2 patients having del17p, 2 t(4;14), 1 t(14;16), and 4 gain 1q. Eight-six percent had 1 line of treatment before enrollment with no patients having prior daratumumab, 14% receiving prior carfilzomib, and 86% having had a prior AHCT a median of 3.6 years (range 0.8-9.3) prior to enrollment. Eighty-two percent underwent AHCT and 59% completed all study treatments. Responses deepened post-AHCT prior to the second 4 cycles of Dara-KRD in most cases. Best overall response on study was a CR in 45% (10/22), >VGPR in 77%, and >PR in 82%. Three patients have died, 1 from infection during the pre-HCT cycles and 2 from disease progression. Conclusion Dara-KRD with salvage AHCT induced high overall response rates, meeting the pre-specified cutoff for promising results. Enrollment is ongoing for the second stage of the study using subcutaneous daratumumab and weekly carfilzomib. Full interim analysis and patient reported outcomes will be presented.