Ankit Kansagra, MD, an assistant professor in the Department of Internal Medicine at UT Southwestern Medical Center and assistant director of the Outpatient Stem Cell Transplant Program, discusses chimeric antigen receptor T-cell agents in the pipeline for multiple myeloma (MM) and how these therapies may impact the treatment landscape pending future approvals.
In part two of this interview with Dr. Kansagra, available December 8, he discusses potential new combination therapy options for MM.
DocWire News: Dr. Kansagra, can you discuss some of the CAR T-cell therapies in development for multiple myeloma, including their targets, clinical trial data that we’ve seen, and your expectations for any future FDA approvals?
Dr. Kansagra: In multiple myeloma, a few of the CAR T-cell therapy targets, which in the most developments, have been the BCMA-targeted CAR T-cell therapies. Those have been most exciting because they have made it to the phase I to phase II trials, especially the registrational studies from Celgene or Bluebird, BMS, the bb2121 compound or the Janssen compound 4538, being farthest out in the clinical development for CAR T-cell therapy. There are certainly a few other CAR T-cell therapies for multiple myeloma, which have grown, and they’re probably in the earlier development of therapy. An example being the CD38 CAR T-cell therapy, the SLAMF CAR T-cell therapy, and GPR5CD CAR T-cell therapy. Those are the three different targets which are being evaluated as T-cell targets.
DocWire News: How do you see the approval of these CAR T-cell therapy impacting the treatment landscape for multiple myeloma?
Dr. Kansagra: I think it’s going to be a huge improvement in our momentum of our treatment options. We have already seen cell therapy in myeloma have impressive results in terms of the response rates. I think the first important step is you have these patients who have got six or seven different lines of treatment, and now they are getting a novel product or a novel mechanism of action and also novel target and seeing an impressive response rate. That was amazing. That’s step number one.
Step number two is, as we have got further into the clinical development of CAR T-cell therapy, we have seen the safety of these products because that is extremely important that our products are safer.
Then the third thing which we have seen is that long-term follow-ups are not there, but what we have started seeing is that our responses, which could last up to a year or a year and a half for the population, where we would have usually seen maybe barely a response in a matter of months.
I think those are exciting times for our patients with multiple myeloma, where they have failed a lot of therapies. I think the more exciting times are going to come when we will start seeing these CAR T-cell therapies, potentially even in earlier lines of treatment options, where they could use maybe as a second-line treatment or as a first-line treatment after stem cell transplant or in lieu of stem cell transplant, maybe we can have deeper and longer remission rates.
DocWire News: With some of these agents potentially coming to market, do you foresee any challenges, either associated with adverse events or the ability to make these treatments widely available to patients?
Dr. Kansagra: Access to care is certainly near and dear to me, and thinking about those challenges is extremely, extremely important. I think we’re going to probably face challenges in a lot of different ways.
The first thing is, obviously, how can we get our patients to the centers who are giving CAR T-cell therapy? How are we going to bring them? We know from our autologous stem cell transplant over the last three to four decades, that still not every eligible transplant patient is referred to a transplant center, for whatever reasons. There are multiple reasons; there are socioeconomic reasons; there are distance reasons. But a lot of them are fixable reasons. There are some which are unfixable, but there are some fixable. I think the first and the foremost important thing is going to be to get our patients to a place who is delivering CAR T-cell therapy. That’s the challenge number one.
Challenge number two is, once they are in there, making sure that they are able to get that thing. So it means they’re not coming too late in their game, so trying to make sure they’re referred in earlier points, so that processes in place, that insurance approval has got started, if we need to work on the sociodemographic issues, how are they going to stay in a particular area? What is the social help, what is the family help they’re going to need? If they had referred earlier on, that’s another, I call it, bottleneck that we need to think of that. That’s where we need to act on it.
The hard thing is obviously the cost. We don’t know what is going to be the cost of the myeloma CAR T-cell therapy, or what is the price of those things. We can certainly estimate that it’s not going to be as cheap given the three CAR-Ts, which are not FDA-approved. I think it’s going to be expensive. You will have to think of the cost of care model of how we are going to work with this.
Last but not least of the challenges are the CAR-T itself. These are in the logistical challenge bucket. Then there are the challenges in the CAR-T landscape or the product itself. We still know that these are second-generation CAR T-cell therapies. They don’t work for everybody. They have a high response rates, but they don’t last that long. We hope to see longer remissions. An example I give, in comparison to large-cell lymphoma, we had 50% of the people who plateaued out, now coming up to about three years. In myeloma, we haven’t obviously made it to three years since the CAR T-cell therapy have started, but we do worry that there is a tail end of the curve that people are already relapsing to it. Obviously, that goes to the product itself or the construct itself, which needs to be developed in multiple different ways. I think of them as two major challenges ahead of us.