When elotuzumab was given in combination with pomalidomide, bortezomib, and dexamethasone (elo-PVD), patients with multiple myeloma refractory to prior treatment demonstrated encouraging responses, according to data from a phase 2 trial presented at the 2019 ASH Annual Meeting by Andrew Yee, MD, from Massachusetts General Hospital Cancer Center in Boston.
This is one of the first multiple myeloma trials to incorporate a monoclonal antibody, an immunomodulatory drug, a proteasome inhibitor, and dexamethasone into a quadruplet regimen.
Elotuzumab has displayed synergistic activity with lenalidomide, pomalidomide, and bortezomib in the treatment of multiple myeloma in previous clinical trials. It is currently only approved for use with lenalidomide and dexamethasone in patients with multiple myeloma who have had between 1 and 3 prior lines of therapy, and with pomalidomide and dexamethasone after 2 prior therapies that included lenalidomide and a proteasome inhibitor.
“Motivated by the above findings, we evaluated the combination of elotuzumab with pomalidomide, bortezomib, and dexamethasone in a phase 2 study,” Dr Yee explained.
To be eligible for the trial, patients had to have relapsed or refractory disease and at least 1 prior line of treatment. Elotuzumab was given once a week for the first two 28-day cycles and then every other week. Pomalidomide was given on days 1 through 21; bortezomib on days 1, 8, and 15; and dexamethasone weekly. The primary outcome was overall response rate (ORR).
Forty-eight patients with a median age of 64 years and a median of 3 prior regimens were enrolled in the trial. All patients had received prior treatment with lenalidomide and a proteasome inhibitor (bortezomib, 96%; carfilzomib, 29%), and were refractory to their last line of therapy. Other prior therapies included autologous stem cell transplant (48%), pomalidomide (33%), daratumumab (25%), and isatuximab (4%).
Best ORR was 61%, with 16 partial responses, 10 very good partial responses, and 2 complete responses in the 46 patients evaluable for response after a median follow-up of almost 19 months. Median progression-free survival (PFS) was 9.8 months.
In the 19 patients who had received only 1 prior line of therapy, outcomes were even more promising: ORR was 74%, and median PFS was not reached.
A benefit was also observed in patients who received prior pomalidomide, carfilzomib, and/or daratumumab; ORR for patients who received prior daratumumab or carfilzomib was 46%, and was 43% for patients who received pomalidomide.
Overall, treatment with the quadruplet was well tolerated, and toxicities were manageable. Grade 3 or worse hematologic adverse events (AEs) included anemia (10%), neutropenia (29%), and thrombocytopenia (15%). Additional common grade ≥3 AEs included lung infection (27%) and hypophosphatemia (15%). Common all-grade nonhematologic AEs were fatigue, upper respiratory tract infection, diarrhea, constipation, hyperglycemia, and sensory neuropathy, with 2 deaths possibly related to sepsis or pneumonia, according to the investigators.
Infectious complications were manageable, and “likely reflect the real-world impact of using a 4-drug combination in a heavily pretreated patient population,” Dr Yee reported. “As upfront and subsequent regimens are increasingly more intensive, newer combinations are necessary to address more challenging-to-treat relapses; elo-PVD is one promising example of such a combination.”