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Triplet Therapy That Includes Elotuzumab Stops Progression of High-Risk Smoldering Multiple Myeloma

Web Exclusives - Conference Correspondent, ASH
Wayne Kuznar

High response rates with the combination of elotuzumab (Empliciti), lenalidomide (Revlimid), and dexamethasone in the treatment of patients with high-risk smoldering multiple myeloma suggest that early intervention may be worthwhile in this patient population, based on results from a phase 2 study, said Irene M. Ghobrial, MD, Attending Physician, Medical Oncology, Dana-Farber Cancer Institute, Boston, at the 2016 American Society of Hematology meeting.

At 24 months, none of the 51 patients who were enrolled in this study showed progression to active disease.

Patients with smoldering multiple myeloma are a heterogeneous population who have approximately a 10% annual risk for disease progression to active multiple myeloma.

“We know that high-risk patients with smoldering multiple myeloma in general have a 50% chance of progression at 2 years,” said Dr Ghobrial.

Lenalidomide plus dexamethasone is effective in patients with high-risk multiple myeloma, and the combination of elotuzumab and lenalidomide has been shown to be safe and effective in patients with relapsed multiple myeloma. Given these data, Dr Ghobrial and colleagues sought to determine the effects of early intervention with the combination of elotuzumab, lenalidomide, and dexamethasone in patients with high-risk smoldering multiple myeloma, specifically whether it could prevent or delay progression to overt disease.

Study Details

Patient eligibility was determined based on the recently defined criteria for high-risk smoldering multiple myeloma. All 51 enrolled patients received weekly elotuzumab (10 mg/kg) on days 1, 8, 15, and 22 for the first two 28-day cycles; lenalidomide on days 1 to 21; and dexamethasone 40 mg on days 1, 8, and 15. Patients then received maintenance therapy with elotuzumab and lenalidomide.

The primary objective was to determine the proportion of high-risk patients with smoldering multiple myeloma who were progression-free at 2 years after receiving the triplet therapy.

Overall, 47 patients were evaluable; 38% had high-risk cytogenetics. The median number of completed treatment cycles was 8 (range, 1-23). In the 23 patients who completed at least 9 cycles of therapy, the overall response rate was 82.6%—the complete response rate was 8.7%, the rate of very good partial response was 26.1%, and the rate of partial response was 47.8%. The clinical benefit rate was 100%. The majority of patients achieved a response by the second cycle. No patients had disease that progressed to active multiple myeloma at 24 months.

The combination was well-tolerated: only 2 patients had grade 4 toxicity (1 with thrombocytopenia and 1 with neutropenia, both of which were reversible). No patient discontinued therapy because of adverse events. Dose reductions were required in 4 patients, 3 of whom were in the maintenance phase.

Preliminary data indicate that progression-free survival may be superior with the triplet therapy compared with lenalidomide plus dexamethasone, said Dr Ghobrial.

“We need long-term follow-up to determine progression-free survival, as well as whether those patients indeed would have delayed end-organ and delayed myeloma events,” Dr Ghobrial emphasized.

Early therapy may inhibit clonal evolution, with the potential to enable cure.

“These patients also have a very good immune system, and therefore immunotherapy…could be very appealing, because it could potentially cure those patients in the early stages,” she said.

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Last modified: April 27, 2020