Top Takeaways from ASCO: Multiple Myeloma

Use of antibodies as single agents and in combination with other therapies is safe, efficacious.

CHICAGO — The efficacy of lenalidomide and dexamethasone for relapsed/refractory multiple myeloma is enhanced with the addition of elotuzumab, while daratumumab shows durable activity in “a heavily pretreated” population of multiple myeloma patients.

Philip McCarthy, MD, professor of oncology at Roswell Park Cancer Institute and professor of internal medicine at the University at Buffalo, discussed the Top Takeaways of these trials, presented at the ASCO 2015 Annual Meeting.

Philip McCarthy

Treating relapsed, refractory multiple myeloma: ELOQUENT-2

The ELOQUENT-2 trial compared the efficacy and safety of elotuzumab, lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed, refractory multiple myeloma who had been treated with up to three prior therapies but were not refractory to lenalidomide.

Patients (n = 646) were randomized 1:1 to elotuzumab, a monoclonal antibody targeting Signaling Lymphocytic Activation Molecule F7, lenalidomide and dexamethasone (n = 321) or lenalidomide and dexamethasone (n = 325). Median age of patients was 66 years and approximately one-third of patients were refractory to their last line of therapy.

Median follow-up for the ELOQUENT-2 trial was 24 months. Median PFS in the elotuzumab-lenalidomide-dexamethasone group was 19.4 (16.6-22.2) months and 14.9 (12.1-17.2) months in the lenalidomide-dexamethasone group (HR = 0.70; 95% CI, 0.57-0.85). At 1 year, PFS was 68% for the elotuzumab-lenalidomide-dexamethasone group and 57% for the lenalidomide-dexamethasone group and 41% and 27% at 2 years. ORR was 79% (95% CI, 74-83) for the elotuzumab-lenalidomide-dexamethasone group and 66% (95% CI, 60-71) for the lenalidomide-dexamethasone group.

“The ELOQUENT trial shows that the combination of lenalidomide, dexamethasone and elotuzumab – when compared to lenalidomide and dexamethasone – gives better responses and better PFS in relapsed, refractory disease,” said McCarthy, who is also director of the Blood and Marrow Transplant Program at Roswell Park Cancer Institute.

Results from phase 2 trial of daratumumab ‘quite exciting’

The phase 2 daratumumab trial, an open-label, international, multi-center study, was conducted in 106 patients treated with 16 mg/kg daratumumab, a human anti-CD38 IgG1κ monoclonal antibody, with a median of five prior treatment lines. Daratumumab was given weekly and changed to monthly after induction and response. Nearly all patients (96%) were refractory to the last line of therapy.

The researchers report a 29.2% ORR (median response duration, 7.4 months) that was consistent across clinically relevant subgroups. Median time to progression was 3.7 months. After a median follow-up period of 9.4 months, 45.2% of responders remain on therapy. At the time of the presentation, median OS had not been reached, but the 1-year estimated OS was 65%.

“The daratumumab trial was a late-breaking abstract, with over 29% response to a single agent in relapsed, refractory multiple myeloma,” McCarthy said. “This is quite exciting.”

Top takeaways

McCarthy anticipates these new therapies – elotuzumab and daratumumab – to be approved in the coming year or year and a half for patients with relapsed, refractory multiple myeloma and incorporated into front-line therapy as well as long-term disease control, particularly in combination with lenalidomide.

“Lenalidomide potentiates the action of the monoclonal antibodies being used to treat multiple myeloma,” he said. “Lenalidomide does a variety of things we don’t completely understand. One of them is that it changes the immune synapse so that it up-regulates immune activity. It also lowers the threshold for natural killer cells to actually have activation. These are all things that make it very enticing to use these antibodies together with an immunomodulatory drug.” – by Julia Ernst, MS

References:

Lonial S, et al. Abstract LBA8512.

Lonial S, et al. Abstract 8508.

Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosures: McCarthy reports serving on advisory boards and as a consultant for Bristol-Myers Squibb, CardioPharm, Celgene, Janssen and Sanofi.