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

JHOP Web Exclusives - Conference Correspondent, ASH 2016 - Roundup
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.

Related Items
NCCN Updated Guideline Adds Treatment Options for HER2-Positive Breast Cancer, Emphasizing CDK4/CDK6 Inhibition in Hormone-Sensitive Disease
Wayne Kuznar
TOP Web Exclusives published on August 15, 2018 in NCCN News
NCCN Issues First Guideline for Immunotherapy-Related Adverse Events
Wayne Kuznar
JHOP Web Exclusives published on August 10, 2018 in Immunotherapy
Regorafenib Dose-Escalation Strategy Potentially a New Standard in Metastatic Colorectal Cancer
Wayne Kuznar
TOP - August 2018, Vol 11, No 2 published on August 3, 2018 in Colorectal Cancer
Immunotherapy Combination Shows Durable Responses in Mismatch Repair–Deficient Metastatic Colorectal Cancer
Wayne Kuznar
TOP - August 2018, Vol 11, No 2 published on August 3, 2018 in Immunotherapy
A Dynamic FDA Has Led to More Rapid Cancer Drug Development
Wayne Kuznar
JHOP Web Exclusives published on July 17, 2018 in FDA Approvals, News & Updates
Palliative Care Use Dismal Among Patients with Hematologic Malignancies
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ASH, Palliative Care, Hematologic Cancers
Oral Multiple Myeloma Medication Linked to Decreased Productivity Loss
Chase Doyle
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ASH, Multiple Myeloma
Ivosidenib, New IDH1 Inhibitor, Elicits Complete Response in Relapsed Acute Myeloid Leukemia
Wayne Kuznar
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, Drug Updates & News, ASH
“Superhero” Navigators Convene at the 8th Annual Navigation & Survivorship Conference
Meg Barbor, MPH
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, AONN+ News
Silent Patients Find Their Voices Through an Advocate’s Journey
Meg Barbor, MPH
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Patient Advocacy, Conference Correspondent, ESMO
Last modified: March 3, 2017