Treatment with the monoclonal antibody elotuzumab, when given in combination with pomalidomide, bortezomib, and dexamethasone (elo-PVD), showed encouraging responses in patients with multiple myeloma (MM) refractory to treatment, according to data from a phase 2 trial. This is one of the first trials of a quadruplet regimen in relapsed and refractory MM to incorporate a monoclonal antibody with an immunomodulatory drug, a proteasome inhibitor, and dexamethasone.
Elotuzumab is currently approved for use with lenalidomide and dexamethasone in MM patients with 1 to 3 prior lines of therapy, and with pomalidomide and dexamethasone after 2 prior therapies including lenalidomide and a proteasome inhibitor.
Elotuzumab has also demonstrated synergistic activity, enhancing the activity of lenalidomide, pomalidomide, and bortezomib in MM. Further adding to the rationale for this trial, a recent study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone when compared with bortezomib and dexamethasone alone in relapsed or refractory MM (Richardson PG, et al. Lancet Oncol. 2019).
“Motivated by the above findings, we evaluated the combination of elotuzumab with PVD in a phase 2 study,” said presenting author Andrew J. Yee, MD, from Massachusetts General Hospital Cancer Center in Boston.
Patients with relapsed or refractory disease who had received at least 1 prior line of treatment were enrolled in the trial. The primary outcome was overall response rate (ORR). Elotuzumab was given weekly 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 was given weekly.
A total of 48 patients with a median age of 64 years and a median of 3 prior regimens received treatment. All patients had 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%).
After a median follow-up of 18.8 months, 16 patients remain on the study (27 patients discontinued for progressive disease, 3 for adverse events [AEs], 1 patient underwent transplant, and 1 patient was lost to follow-up).
Of 46 patients evaluable for response, best ORR was 61%, with 16 partial responses, 10 very good partial responses, and 2 complete responses. Median progression-free survival (PFS) was 9.8 months.
In the 19 patients who received only 1 prior line of therapy, ORR was 74% and median PFS was not reached.
Patients who received prior pomalidomide, carfilzomib, and/or the anti-CD38 monoclonal antibody daratumumab also benefited: ORR for patients who received prior daratumumab or carfilzomib was 46%, and was 43% for patients who received pomalidomide.
Treatment was well-tolerated, and toxicities were manageable. Grade ≥3 hematologic 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.
“With the limitations of cross-trial comparisons and small patient numbers, for patients with 1 prior line of treatment and refractory disease, a PFS at 18 months of 68% with elo-PVD compares favorably with a median PFS of 17.8 months in a similar lenalidomide-refractory subgroup of PVD in the OPTIMISMM trial,” said Dr Yee. “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.”
Yee AJ. ASH Abstract 3169.