The addition of elotuzumab to a standard three-drug induction regimen did not improve outcomes in patients with high-risk multiple myeloma enrolled in the randomized phase II SWOG S1211 trial, according to findings reported during the ASCO20 Virtual Scientific Program by Saad Zafar Usmani, MD, FACP, of Levine Cancer Institute/Atrium Health, Charlotte, North Carolina.¹

Saad Zafar Usmani, MD, FACP

“In the first randomized high-risk multiple myeloma study reported to date, the addition of elotuzumab to lenalidomide/bortezomib/dexamethasone [RVd] induction and maintenance did not improve patient outcomes,” Dr. Usmani reported.

The S1211 trial randomly assigned 134 patients with newly diagnosed high-risk myeloma to RVd with or without elotuzumab at 10 mg/kg on days 1, 8, and 15. Induction consisted of eight 21-day cycles. Maintenance continued indefinitely with all RVd drugs given at lower doses and elotuzumab still administered at 10 mg/kg. The primary endpoint was progression-free survival.

The study hypothesized that the addition of elotuzumab could overcome high-risk features. High risk was defined by a poor-risk score on gene-expression profiling, one or more cytogenetic abnormalities, primary plasma cell leukemia, or elevated levels of serum lactate dehydrogenase (two times higher than the institutional upper limit of normal).

No Improvement in Progression-Free or Overall Survival

After 53 months’ median follow-up, the addition of elotuzumab did not increase progression-free or overall survival. Median progression-free survival was 34 months with RVd and 31 months with RVd plus elotuzumab (P = .449). Median overall survival was not reached with RVd and was 68 months with RVd/elotuzumab (P = .239). “The median progression-free survival and overall survival seen in both arms of the study exceeded the original statistical assumptions,” Dr. Usmani pointed out.

Response rates were also not significantly different: 88% with RVd and 83% with RVd/elotuzumab. The elotuzumab arm experienced more grade > 3 infections (16% vs 8%) and more peripheral neuropathy (13% vs 8%).

“This was the first randomized study evaluating the role of a monoclonal antibody in high-risk multiple myeloma. Although no benefit was found for elotuzumab, the study does support the role of a proteasome inhibitor plus immunomodulatory agent as maintenance therapy in this patient population,” Dr. Usmani said. “The data will serve as a benchmark for future randomized, high-risk myeloma trials.” 

DISCLOSURE: Dr. Usmani has served as a consultant or advisor for AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Seattle Genetics, SkylineDx, and Takeda; has served on speakers bureaus for Amgen, Celgene, Janssen Oncology and Takeda; and has received research funding from Amgen, Array BioPharma, Bristol-Myers Squibb, Celgene, Janssen Oncology, Pharmacyclics, Sanofi, and Seattle Genetics.

REFERENCE

1. Usmani SZ, Ailawadhi S, Sexton R, et al: Primary analysis of the randomized phase II trial of bortezomib, lenalidomide, dexamethasone with/without elotuzumab for newly diagnosed, high-risk multiple myeloma (SWOG-1211). ASCO20 Virtual Scientific Program. Abstract 8507.