Dr Yael Cohen Explains the Barriers to Accessing Triplet Combination Therapies for MM


More data is emerging on the efficacy of several triplet therapies to treat single-class refractory multiple myeloma (MM), potentially giving patients more therapy options than ever before, according to Tel-Aviv Sourasky Medical Center's Yael Cohen, MD, at the European Hematology Association 2023 Congress.

Yael Cohen, MD, vice president of clinical development at VBL Therapeutics and a senior physician in the hematology department at Tel-Aviv Sourasky Medical Center, dived into barriers to access for triplet combinations therapies used to treat multiple myeloma at the European Hematology Association 2023 Congress.


What challenges or barriers do patients with single-class refractory multiple myeloma face in achieving a positive treatment response?

So patients in this day and age that have single-class refractory [MM] are typically lenalidomide refractory and this is because most patients today are treated with a [lenalidomide]-based upfront treatment and with long-term lenalidomide so that when they are relapsing, if they are single-drug refractory, it is usually the lenalidomide component—both in the transplant-eligible patients that would typically continue with lenalidomide maintenance after the transplant and also, with the transplant ineligible, the older patients, they will also get some combination at their [treatment] induction and they might be on long-term lenalidomide.

I just want to remark here that going forward, we're probably going to see less patients who were single-class refractory [MM]. We know that for elderly patients, they are getting a DRd [daratumumab and lenalidomide] combination therapy continuing with lenalidomide and daratumumab. So, they will already have 2 drugs [they are refractory to] if they relapse, just as an example.

But if we get back to the lenalidomide-treated refractory patients, in order to have a good response for their next line of treatment when they are a relapsing, of course, we will want to avoid lenalidomide since they are refractory, and we can look at moving to a PI [proteasome inhibitor]-based day regimen including an anti-CD38 drug in the regimen and switching lenalidomide to a more advanced IMiD [immunomodulatory drugs] such as pomalidomide. So, there are many triplets therapies out there that have been investigated in clinical trials.

Probably the most effective regimen and most effective triplets that are less effective from the lenalidomide refractoriness of the patients, as far as the outcomes, are those that combined a CD38 antibody, either daratumumab or isatuximab together with carfilzomib and dexamethasone. They really show a very nice progression-free survival with figures of over 30 months, and again, quite similar, even if you have refractory MM, but of course there are many other triplets out there that can be used in various patients with pomalidomide, bortezomib, and ixazomib with either of the anti-CD38 antibodies.

But certainly, this is a challenge, these lenalidomide-treated refractory patients, because they are certainly an unmet medical need in this day and age. They have worse outcomes than their peers and the data shows that most patients who are exposed to lenalidomide, a vast majority of them are actually refractory to lenalidomide.

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