|A tri-reagent regimen for multiple myeloma|
|Multiple myeloma patients treated with immunomodulatory agents and proteasome inhibitors, which have experienced relapse or refraction, suffer a poor prognosis. It has been reported that the combination of elotuzumab (a humanized immunostimulatory IgG1 monoclonal antibody), lenalidomide (an immune-modulating drug) and dexamethasone reduced the chance of progression or death in multiple myeloma patients by 30% as a second-line treatment. Pomalidomide has a similar structure and feature as lenalidomide, and also presents other biological functions. Pomalidomide combined with dexamethasone has been approved for therapy of multiple myeloma patients who have failed at least two previous therapies. It has been proposed that the combination of elotuzumab and pomalidomide might improve the outcome of multiple myeloma patients who are refractory to lenalidomide or experience recurrence after lenalidomide treatment, via promoting immune cell-mediated tumor cell killing. In a recent paper in the New England Journal of Medicine (here), the efficacy and safety of the triple-medication regime of elotuzumab, pomalidomide, and dexamethasone in recurrent or refractory multiple myeloma patients were determined in a phase 2 randomized trial (the ELOQIENT-3 trial).
Adult multiple myeloma patients--with failure in two or more cycle of therapy including at least two consecutive cycles of lenalidomide and a proteasome inhibitor (alone or combined) --whose disease was refractory to lenalidomide or relapsed after lenalidomide administration, were recruited in the trial. A total of 117 patients were involved in this trial, among whom 60 patients were randomly assigned to the elotuzumab group (receiving the combination of elotuzumab, pomalidomide, and dexamethasone), and 57 participants were assigned to the control group (receiving pomalidomide and dexamethasone). All patients received prophylactic therapy for thromboembolism.
Patients in the elotuzumab group demonstrated a longer progression-free survival compared to those in the control group (10.3 months v.s. 4.7 months). Patients in the elotuzumab group harbored a smaller risk of recurrence or death which was only 54% of that in the control group, indicating the combined treatment reduced the risk of recurrence or death by 46%. Moreover, the elotuzumab group had a response rate (partial response and complete response) of 20%, whereas the control group had a response rate of 9%. Grade 3 or 4 adverse events were observed in 57% of the patients in the elotuzumab group and 60% of those in the control group, among which neutropenia, anemia, and hyperglycemia were most common. Infection rates were comparable between the two groups (65% in both groups). Rates of discontinuation of treatment were similar between the two groups, due to adverse events (18% in the elotuzumab group, 24% in the control group) and infection (7% in the elotuzumab group, 5% in the control group).
This trial concludes that the patients with multiple myeloma that are refractory to lenalidomide or relapsed after lenalidomide treatment demonstrate survival benefit and a higher response rate if treated with the combination of elotuzumab, pomalidomide, and dexamethasone, compared to patients receiving pomalidomide and dexamethasone. The tri-reagent regimen did not show increased rates of adverse events.
This trial was supported by a pharmaceutical company.