NEW YORK (Reuters Health) – More than 80% of patients with advanced multiple myeloma responded to elotuzumab plus lenalidomide and low-dose dexamethasone in a phase I study.
“I am a great believer of combination therapy, and in order to have successful combinations, one needs agents that can be combined safely,” Dr. Sagar Lonial from Emory University, Atlanta, Georgia told Reuters Health in an email. “The safety and efficacy of the combination in our phase I study is quite striking, and with the activity of the combination, it represents a great new hope for patients.”
Elotuzumab is a humanized monoclonal immunoglobulin G1 antibody targeting CS1, a surface glycoprotein highly expressed on MM cells. Dr. Lonial and colleagues tested it in combination with lenalidomide and low-dose dexamethasone in 29 patients with refractory or relapsed MM.
The primary objective was to identify the maximum-tolerated dose of elotuzumab in this combination, but the investigators also evaluated efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics, reporting their findings online April 30th in the Journal of Clinical Oncology.
There were no dose-limiting toxicities, and the maximum-tolerated dose was not reached up to the maximum proposed dose of 20 mg/kg. Adverse events reported in at least 39% of patients included fatigue, anemia, diarrhea, nausea, constipation, and neutropenia. All but four patients had at least one infusion reaction.
Refinement of the premedication regimen in the phase II study appears to mitigate the elotuzumab-related infusion reactions, the researchers note.
Twenty-three (82%) of 28 patients who actually received treatment achieved an objective response, including nine patients (32%) who achieved at least a very good partial response. The median time to response was 50 days.
All but one patient with no prior exposure to lenalidomide (21/22, 95%) achieved at least a partial response, compared with only two of six patients (33%) with prior exposure to lenalidomide. Even among the 12 patients who were refractory to their most recent therapy, 10 (83%) achieved a partial response or better with the combination.
Because 15 patients remain on treatment without disease progression, the medians of response duration and time to progression have not been reached after a median of 16.4 months of follow-up.
“I think the idea of having an antibody to treat myeloma is very exciting,” Dr. Lonial said. “Many other cancers have relatively ‘non-toxic’ antibodies that help to improve outcomes, and in myeloma while we have had many advancements, we do not have an antibody. Use of the antibody for newly diagnosed, relapsed, and maintenance therapy gives great opportunity and hope for patients.”
“Similar to non-Hodgkin lymphoma, where rituximab is used in many different settings and has improved outcomes, we hope to use elotuzumab in combination with lenalidomide/dexamethasone to improve depth of response and duration of response,” Dr. Lonial concluded.
“The phase II trial has been reported on several times now,” Dr. Lonial said. “Basically it showed a similar response rate, and that the progression free survival appears to be on par with what we showed in the phase I study.”
The study was supported by Abbott Biotherapeutics, which employs three of the paper’s 12 authors and has financial relationships with Dr. Lonial.
J Clin Oncol 2012.