Another exciting multiple myeloma treatment will be presented at the 2015 ASCO Annual Meeting,” Philip L. McCarthy, MD, Professor of Oncology and Director of the Blood and Marrow Transplant Center at Roswell Park Cancer Institute, Buffalo, New York, commented in an interview with The ASCO Post. “ELOQUENT-2 is the first phase III trial to examine a monoclonal antibody, elotuzumab, for the treatment of relapsed and refractory multiple myeloma.” 

Preclinical studies had suggested that bortezomib (Velcade) or lenalidomide (Revlimid) plus elotuzumab would be superior to either drug alone.¹ However in the clinic, the combination of bortezomib and elotuzumab did not appear to generate responses comparable to those with lenalidomide, elotuzumab, and dexamethasone,^2,3 Dr. McCarthy pointed out.

Previous preclinical work had demonstrated that lenalidomide influences the immune synapse between lymphoma cells and T cells.^4,5 “This may, in part, explain the efficacy of lenalidomide when combined with antibodies for the treatment of multiple myeloma.  Lenalidomide potentiates the monoclonal antibody antitumor activity, as was demonstrated with rituximab [Rituxan] in a preclinical lymphoma model,” he explained.

How will the clinician approach the use of elotuzumab for clinical use when it becomes readily available? For one thing, Dr. McCarthy said, since elotuzumab has limited efficacy as a single agent,⁶ it must be partnered with lenalidomide and dexamethasone. The other question will be how this regimen compares with other novel high-efficacy regimens, he said.

Comparison With ASPIRE Data

“It will be critically important to contrast the published results, when available, to the ASPIRE trial,⁷ which examined carfilzomib [Kyprolis], lenalidomide, and dexamethasone vs lenalidomide/dexamethasone for relapsed and refractory multiple myeloma,” he suggested. In ASPIRE, the progression-free survival was significantly improved with the carfilzomib regimen: 26.3 months vs 17.6 months without carfilzomib, which is “somewhat different” than the median progression-free survival of 19.4 vs 14.9 months in this study, he pointed out.

But, he noted, the ASPIRE trial patient population appeared to contain a lower percentage of high-risk cytogenetic patients (31.5%) compared with ­ELOQUENT-2 (41%). The proportion of patients with refractory disease may also differ. During the press briefing, Dr. ­Lonial acknowledged that the patient populations were very different, including more refractory patients and more with high-risk genetics in ELOQUENT-2.

Dr. McCarthy said that the combination of elotuzumab with lenalidomide and dexamethasone may overcome lenalidomide resistance, “but this will depend on the reporting of results and subset analyses. With the ongoing development of anti-CD38 antibodies,   … we will have multiple options for relapsed and refractory multiple myeloma and eventually for upfront therapy. Future studies will determine how monoclonal antibodies will advance the long-term control of multiple myeloma,” he said. ■

Disclosure: Dr. McCarthy serves on advisory boards and is a consultant for Bristol-Myers Squibb, Celgene, Millenium Takeda, Sanofi, Janssen, and Karyopharm.

References

1. Tai YT, et al: Blood 112:1329-1337, 2008.

2. Jakubowiak AJ, et al: J Clin Oncol 30:1960-1965, 2012.

3. Lonial S, et al: J Clin Oncol 30:1953-1959, 2012.

4. Ramsay AG, et al: Blood 114:4713-4720, 2009.

5. Hernandez-Ilizaliturri FJ, et al: Clin Cancer Res 11:5984-5992, 2005.

6. Zonder JA, et al: Blood 120:552-559, 2012.

7. Stewart AK, et al: N Engl J Med 372:142-152, 2015.