Ajai Chari, MD
Daratumumab (Darzalex) was shown to be safe and effective when added to the backbone of carfilzomib (Kyprolis) and dexamethasone in an analysis of patients with relapsed/refractory multiple myeloma enrolled on the phase Ib MMY1001 trial. Findings presented during the 2018 ASCO Annual Meeting signaled promising efficacy in patients who are refractory to lenalidomide (Revlimid), according to lead study author Ajai Chari, MD.
In this subgroup from MMY1001, 51 lenalidomide-refractory patients were treated with daratumumab plus carfilzomib and dexamethasone. At a median follow-up of 12.0 months, the median progression-free survival (PFS) in the lenalidomide-refractory population was 14.1 months (95% CI, 12.0-NE) and the 12-month PFS rate was 62%. Additionally, the overall response rate was 79%, including a complete remission (CR) rate of 10% and a stringent CR rate of 8%.
Chari also presented early findings from the PAVO study at the 2018 ASCO Annual Meeting, which is a phase I study evaluating subcutaneous daratumumab in patients with relapsed/refractory myeloma. This trial is aiming to cut down on infusion-related reactions for patients undergoing treatment with daratumumab.
In an interview with OncLive®
, Chari, associate professor, Mount Sinai Hospital, discussed the addition of daratumumab to carfilzomib and dexamethasone, as well as the potential impact of subcutaneous daratumumab in the treatment of patients with myeloma.
OncLive: Can you begin by giving some background information on MMY1001?
: The purpose of MMY1001 was to show the safety of adding daratumumab to various myeloma backbone regimens. In this particular subgroup, there was an addition of daratumumab to carfilzomib and dexamethasone.
The study showed that the addition of daratumumab did not add much to the safety profile of these other regimens. There was no synergistic or increased toxicity, with the only possible caveats being infusion-related toxicities from the monoclonal antibody administration. In some studies, there is a slightly higher rate of neutropenia, but typically without any associated increase in infections.
What was the rationale for the analysis?
The rationale for the subgroup analysis—to look at the lenalidomide-refractory population—is basically coming from the fact that there is an increase in the use of lenalidomide maintenance after induction therapy and transplant due to the overall survival benefits reported. This means that the multiple large phase III studies that were published in high-impact journals, comparing triplet novel regimens with doublet control arms of lenalidomide/dexamethasone, would not apply to most patients who are refractory to these 2 agents. [In our study], we looked at patients who were refractory to lenalidomide see what the efficacy might be.
The overall population in this subgroup was 85, of whom approximately 50 were refractory to lenalidomide. What we saw was that the response rate did not seem to differ in the 2 groups, at around 80%. Most interestingly, the PFS was 14 months for the lenalidomide-refractory population. Admittedly, it has not been reached in the overall population but, even for lenalidomide-refractory groups, that is very impressive.