Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

Abstract

BACKGROUND:

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.

METHODS:

In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival.

RESULTS:

Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients.

CONCLUSIONS:

Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).

• Authors: Sagar Lonial, Meletios Dimopoulos, Antonio Palumbo, Darrell White, Sebastian Grosicki, Ivan Spicka, Adam Walter-Croneck, Philippe Moreau, Maria-Victoria Mateos, Hila Magen, Andrew Belch, Donna Reece, Meral Beksac, Andrew Spencer, Heather Oakervee, Robert Z Orlowski, Masafumi Taniwaki, Christoph Röllig, Hermann Einsele, Ka Lung Wu, Anil Singhal, Jesus San-Miguel, Morio Matsumoto, Jessica Katz, Eric Bleickardt, Valerie Poulart, Kenneth C Anderson, Paul Richardson, ELOQUENT-2 Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 373 Issue 7 Pg. 621-31 (Aug 13 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 26035255 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Receptors, Immunologic
• SLAMF7 protein, human
• Signaling Lymphocytic Activation Molecule Family
• elotuzumab
• Thalidomide
• Dexamethasone
• Lenalidomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Dexamethasone (therapeutic use)
• Disease-Free Survival
• Humans
• Lenalidomide
• Middle Aged
• Multiple Myeloma (drug therapy, mortality)
• Receptors, Immunologic (antagonists & inhibitors)
• Recurrence
• Signaling Lymphocytic Activation Molecule Family
• Thalidomide (analogs & derivatives, therapeutic use)