Targeting CD38 in Relapsed/Refractory Multiple Myeloma - Episode 3
Paul G. Richardson, MD:In the context of what we do after lenalidomide has failed a patient, what options do we have? Well, the very good news is we have multiple options. And most importantly, we have high-level evidence to support them. It’s important to recognize that previous phase III studies in relapsed/refractory disease often used lenalidomide as a control arm. Therefore, the exposure of lenalidomide in the study groups was minimal, or in fact, excluded in many cases.
Now with lenalidomide being a standard of care for both upfront and maintenance therapy, we have to embrace and understand how to respond to lenalidomide failure. In patients for whom lenalidomide has failed, we then think of pomalidomide as an ideal platform. Why? Because the level of evidence for it is so good now. This year we published the phase III randomized trial, OPTIMISMM, which is a real-world study looking at pomalidomide, bortezomib, and dexamethasone versus the control group of bortezomib and dexamethasone for PFS [progression-free survival], OS [overall survival], and all of the usual secondary end points. And in a nutshell, we were able to demonstrate substantial PFS benefit, but only for the trial overall by intent to treat. But most importantly, in the first relapse group, we saw a striking PFS benefitexceeding 20 months median for patients who were lenalidomide-exposed.
And if we looked specifically at the lenalidomide-refractory group in that population, we saw that that PFS gain was sustainedapproaching 18 months. So clearly, the use of the 3-drug platform is a powerful option to have in that setting, and pomalidomide should be the backbone.
Beyond pomalidomide, I think it’s very important to note that there are other options that can be rationally combined. We have now the daratumumab data supporting the use of daratumumab when pomalidomide is needed. We also importantly have excellent data integrating carfilzomib into this platform. And especially for patients who are fit and well and don’t have underlying cardiovascular risk, that, to me anyway, is a very important choice, especially in patients with high-risk disease.
I think one of the most exciting pieces of data that we’ve had at this meeting, and also previously at ASCO [American Society of Clinical Oncology] and EHA [European Hematology Association annual meetings in 2019], has been the results of the ICARIA-MM trial. This particular trial looked at the combination of pomalidomide with the new CD38 antibody, isatuximab, and showed striking clinical benefit in favor of isatuximab, pomalidomide, and dexamethasone compared to pomalidomide and dexamethasone alone. What was very interesting was to see its benefit in the high-risk population, and also in the frailer and elderly population. This was very much a real-world study, and provided us by virtue of that, a wealth of information.
Transcript edited for clarity.