Elotuzumab plus standard treatment benefited multiple myeloma patients12 Jun 2015
Patients with relapsed and refractory myeloma had significant improvement in progression-free survival (PFS) with the monoclonal antibody elotuzumab added, according to a study.
Elotuzumab targets signaling lymphocytic activation molecule F7 (SLAMF7), which is selectively expressed on myeloma and natural killer (NK) cells but not normal tissues. Elotuzumab has a twofold mechanism: direct killing of myeloma cells and activation of NK cells. Collectively, the effects enable killing of myeloma cells without collateral damage to normal cells.
A clinical trial with patients from 224 sites around the world
Meletios Dimopoulos, MD, of the University of Athens in Greece reported findings from a randomized, phase 3 trial comparing lenalidomide-dexamethasone with or without elotuzumab in patients with relapsed or refractory myeloma and a treatment history of one to three prior myeloma regimens.
Primary data analysis included 626 patients, enrolled and randomized at 224 sites around the world. The treatment groups had no major differences in baseline characteristics. About a third of patients had exhibited resistance to their most recent therapy, including bortezomib in 22% and thalidomide in 10%.
After the analysis of the results, Dimopoulos reported that:
- After a median follow-up of 24.5 months, the elotuzumab group had a 30% reduction in the hazard for death or progression versus the control arm.
- The median PFS was 14.9 months with lenalidomide (Revlimid) and dexamethasone, increasing to 19.4 months when elotuzumab was added to therapy. Objective response rate increased significantly with elotuzumab.
- Elotuzumab-treated patients had an overall response rate of 79% compared with 66% for patients who received only lenalidomide and dexamethasone.
- The magnitude of the PFS difference between treatment groups increased with follow-up.
- The 1-year PFS was 68% in the elotuzumab arm and 57% in the control group.
- The 2-year PFS was 41% and 27%, respectively, for the elotuzumab and control groups.
- At data cutoff, 35% of elotuzumab-treated patients remained on therapy compared with 20% of the control group.
- The PFS benefit was consistent across major subgroups.
“No obvious detrimental effect on quality of life”
Adverse events were consistent with known effects of lenalidomide and dexamethasone, and the only noteworthy new events associated with elotuzumab were injection-site reactions, according to study author.
A quality-of-life assessment showed that patients were most bothered by pain and fatigue at baseline. The treatment groups did not differ with respect to change in pain severity or interference with daily living. The addition of elotuzumab to the lenalidomide-dexamethasone combination had no obvious detrimental effect on quality of life, as assessed by a standard instrument.
"The trial represents the highest level of evidence for this novel target and agent in the treatment or relapsed or refractory multiple myeloma," Dimopoulos said. "Patients who received elotuzumab had a higher overall response rate and duration of remission without a significant increase in side effects. These data confirm the unique mechanism and new target as being important in the management of multiple myeloma," he added.Source: MedPage Today