Daratumumab and elotuzumab are monoclonal antibodies approved by the FDA in November 2015 for the treatment of relapsed/refractory multiple myeloma (RRMM). Daratumumab was approved as a single therapy targeting plasma cell surface CD38, while elotuzumab was approved as part of combination therapy (with lenalidomide), targeting SLAMF7 to impact natural killer cell activation. While both therapies are involved in the recruitment of cellular cytotoxic mechanisms against multiple myeloma, the efficacy of each after a patient has relapsed on the other therapy is unclear.
We conducted a retrospective analysis of 26 patients with RRMM at the University of Miami Sylvester Comprehensive Cancer Center that received both elotuzumab and daratumumab between January 2016 and December 2018 to determine if progression-free survival (PFS) with each monoclonal antibody is affected by previous treatment with the other. Median age at time of treatment was 59.7 years, and 58% of patients were female. Median number of treatments prior to first monoclonal antibody was 4, and median time to first monoclonal antibody was 58 months. Seventeen patients received daratumumab prior to elotuzumab, while nine patients received elotuzumab prior to daratumumab. Patients that received daratumumab first received on average 2 treatments before receiving elotuzumab, while patients receiving elotuzumab first received 1 treatment on average before receiving daratumumab, and time between treatments was significantly shorter for patients receiving daratumumab first (3.7 months vs. 12.4 months, p = 0.0009). Overall survival (OS) and cumulative PFS trended higher in patients receiving elotuzumab first but did not reach significance (OS 37 months vs. 21.7 months, p = 0.07, and PFS 15.5 months vs. 7.6 months, p = 0.09). PFS with initial elotuzumab was higher than with initial daratumumab (11.9 months vs. 3.5 months, p = 0.0124). PFS on daratumumab trended favorably when elotuzumab was administered first (9.4 months vs. 3.0 months), although not significant (p = 0.19). In patients receiving daratumumab, 47% initially demonstrated response, all with eventual progression, with 40% responding to later elotuzumab therapy. Conversely, 56% of patients receiving elotuzumab first demonstrated a response, with 44% eventually progressing over time, and 56% responding to subsequent daratumumab therapy.
These results generate a plausible hypothesis related to a possible potentiating effect of elotuzumab that extends after therapy regimen has changed and warrants further investigation into the sequencing of these two therapies in RRMM and the interplay of their different immunologic impact.
Hoffman:Seattle Genetics: Research Funding; Loxo: Current equity holder in publicly-traded company; Celgene: Honoraria, Speakers Bureau.
Asterisk with author names denotes non-ASH members.