Effect of Timing of Monoclonal Antibody Therapy on the Time to Next Treatment and Response Rate in Heavily Pre-Treated Patients with Myeloma Who Separately Received Both Daratumumab and Elotuzumab-Based Regimens

Introduction Notable advances have been made in multiple myeloma management (MM) in recent years. The monoclonal antibodies daratumumab (dara) and elotuzumab (elo) are integral in the management of relapsed/refractory MM and are moving into the frontline setting for transplant ineligible patients. Despite many trials evaluating the efficacy of these agents, there is no consensus on the optimal integration of these agents into the current paradigm of MM management. There is a paucity of data to guide the selection of one antibody over the other, and little is known about whether the use of one prior antibody alters the efficacy of other agents in subsequent lines of therapy. We retrospectively analyzed MM patients treated with both elo and dara during the course of their disease to assess whether the sequence of elo followed by dara or dara followed by elo led to better outcomes. Methods We reviewed the records of MM patients ≥ 18 years old who received both dara and elo at any time during treatment at MD Anderson Cancer Center. We evaluated the time to next treatment (TTNT), defined as the start date of one treatment to the start of the next treatment, and the overall response rate (ORR) (partial response or greater) to dara and elo. TTNT and ORR were calculated for dara when administered as the first antibody during treatment and to dara when administered as the second antibody (elo given during prior lines of treatment). We evaluated TTNT and ORR when elo was administered as the first antibody during treatment and to elo when administered as the second antibody (dara given during prior lines of treatment). The association with categorical patient variables (age, race, immunoglobulin class, number of prior lines of therapy, agent co-administered with the second monoclonal antibody given) was analyzed using Fisher exact tests. Outcomes were estimated using the Kaplan-Meier method and differences in survival among groups were assessed using two-sided log-rank tests. Results We identified 56 patients treated with both dara and elo. We excluded 6 for missing data; 56% of the 50 patients were male; 70% were Caucasian; 56% with IgG subclass paraprotein; 66% kappa light chain restricted. Patients were heavily pre-treated; most with >5 lines of therapy prior to initiation of dara or elo. Elo was the first agent received in 64% of patients. Independent of treatment order, the ORR to elo and dara were 72% and 88% respectively. When elo was administered prior to dar