A maintenance regimen of lenalidomide (Revlimid) and elotuzumab (Empliciti) after autologous stem cell transplant (ASCT) improved the quality of responses achieved with induction therapy in patients with multiple myeloma.
In a phase 2 study, 36% of patients receiving the combination as maintenance showed an improvement in response, and 20% of patients converted either to a complete response (CR) or stringent CR (sCR). The study is ongoing, with a planned accrual of 100 patients. The study data and results were reported by Sheeba K. Thomas, MD, MS, Associate Professor, Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX, at ASH 2017.
“The number of patients achieving CR may in fact be underestimated due to elotuzumab interference with electrophoretic measurements,” said Dr Thomas. “Nineteen of 33 patients not achieving CR had GK paraproteins, and 17 of the 19 were in VGPR [very good partial response].”
After the enrollment of 68 patients who have been followed for a median of 23 months, the median progression-free survival (PFS) had not been reached. The 2-year estimated PFS was 88%. The median overall survival also had not been reached.
The study evaluated elotuzumab plus lenalidomide as maintenance therapy after myeloablative ASCT was evaluated in patients treated with ≤2 lines of systemic therapy before ASCT. The first 28 patients received elotuzumab 10 mg/kg weekly for cycles 1 and 2 and bimonthly for cycles 3 through 6, followed by 20 mg/kg monthly from cycle 7 forward.
The study was amended for patients to receive elotuzumab 20 mg/kg monthly during cycles 3 through 6. Patients aged <75 years were instructed to take dexamethasone 28 mg before infusion for cycles 1 and 2. The dose was reduced to 8 mg for patients aged ≥75 years in an effort to optimize tolerability. All patients received 4 to 10 mg of intravenous dexamethasone immediately before each infusion.
Patients received lenalidomide 10 mg daily for cycles 1 through 3, which could be increased to 15 mg daily from cycle 4 forward in the absence of significant cytopenias and nonhematologic toxicity. In all, 44% of patients required dose reductions of lenalidomide “so that most of our patients are currently dosed at 10 mg on days 1 through 21 of the 28-day cycle due to intolerability,” Dr Thomas said.
Overall, 71% of the patients received 1 line of induction therapy before ASCT, and 29% received 2 lines. A 3-drug induction regimen was used in all but 2 patients, with the most common (72%) being a proteasome inhibitor plus lenalidomide and dexamethasone. The median time from ASCT to the start of study treatment was 158 days.
A total of 31% of patients had high-risk cytogenetics according to the International Myeloma Working Group criteria. The high-risk cytogenetic features included deletion 17p in 10% and t(4;14) in 7%.
Of the 68 enrolled patients, 25 (36%) had an improvement in their quality of response. Among the patients whose responses were upgraded from study entry, the median number of cycles to best response was 3.5.
Of the 13 patients in CR who were tested for minimum residual disease (MRD), 10 were MRD negative at study entry and 3 converted from VGPR to MRD negative.
The majority (75%) of patients were in VGPR or better at study entry. “This has improved to 91% based on best response estimates on study, including 51% who have achieved CR or sCR,” said Dr Thomas.
A total of 3 patients died, 2 with progressive disease while receiving salvage therapy, and 1 with acute encephalopathy and refractory status epilepticus in VGPR.
Anemia (6%), neutropenia (31%), and thrombocytopenia (7%) were the most common grade ≥3 hematologic toxicities.
The most common nonhematologic adverse events were fatigue (76%), myalgias (71%), diarrhea (69%), respiratory infections (57%), nausea/vomiting (57%), and dizziness (56%).