A Look at the Multiple Myeloma Pipeline

Shaji Kumar, MD, consultant in the Division of Hematology and professor of medicine at Mayo Clinic Cancer Center in Rochester, Minnesota, highlighted treatments of interest in the pipeline for multiple myeloma and how the treatment paradigm may change in the coming years.

Watch part 1 of the interview with Dr. Kumar where he discusses the first approved anti-BCMA therapy.

Watch part 2 of the interview with Dr. Kumar, where he discusses results of the ENDURANCE trial.

DocWire News: What are some other treatments in the pipeline that you’re interested in or excited about for either untreated or relapsed/refractory multiple myeloma?

Dr. Kumar: I think the immunotherapies are probably the most exciting. We have seen now data from the bb2121 from the CARTITUDE trial and the EVOLVE trial. There are multiple different CAR-Ts, a majority of them targeting BCMA that has shown efficacy. We seem to get high overall response rate, deep responses in these highly pre-treated patients. The challenge that we have right now is obviously the fact that some of these patients would still relapse. And especially the patients who don’t respond, have very poor outcomes. So how do we improve the response rate? How do we make the responses more durable? Those are research that’s ongoing right now. CAR-Ts is very exciting.

The second thing would be the T-cell engagers. We saw the data with the Celgene molecule, Janssen, and Amgen and a variety of other ones that are going through clinical trials. But I think the whole platform of T-cell engagement using bispecific antibodies, targeting BCMA and CD3, seems to be a viable strategy. It’s quite exciting. And I think these immunotherapies, both CAR Ts and bispecifics, will move to early on fairly soon. We’ll get a better sense of how that would pan out. Now, the venetoclax data is pretty interesting, especially for the t(11;14) patients, the question is whether we can go beyond t(11;14) and use BCL2 expression as a biomarker for selecting this therapy. Those studies are ongoing. I suspect, yes, but now that probably will be about 30% to 40% of the myeloma patients. So venetoclax may have role both in the beginning and also later on as the disease progresses, and also with other plasma cell disorders that carried t(11;14) translocation.

The other drugs which are obviously interesting, melflufen is an alkylator that is going through clinical trials. And it depends on the fact that it is linked to amyloid that allows it to be mostly active or cleaved within the myeloma cell. So it can be a little bit more tumor-specific, but again, it’s mostly dependent on the cellular metabolism state. Melflufen—we had to see how that pan out, how it combines with other drugs and so forth. That’s where we are with these novel therapies. Obviously, there’s other things in the pipeline to, which I would say very earlier on.

But I should also mention the new IMiDs, like iberdomide, that is being developed. And we have seen some early data showing that it can be quite effective in the refractory patient population. This uses a mechanism that targets the, kind of the same pathway that the IMiDs did, but a little bit more specific and seems to be effective even in patients who have become refractory to IMiD. So there’s a bunch of things going through trials.

DocWire News: How do you see some of these newer agents or potentially to be approved agents impacting the treatment paradigm or guidelines in the next few years?

Dr. Kumar: I think the key thing would be, in the newly diagnosed setting, will quadruplets take over the triplet approach right now? So that’s going to be a key question. The relapse patient population I think will have a lot of choices. So the question is, how do we select one from amongst many, knowing that this is an incurable disease right now? There’s always going to be need for new therapies. So I think it may not at the end of the day matter as much what particular sequence of drugs or combinations we use. But I think some of the general principles we want to try and use that drug that the patient or class of drug that the patient has not been exposed to before and things along those lines would help us make a decision. And obviously the guidelines will change as new drugs get approved, and we figure out where to use them to the maximum effect.