CAR T-Cell Therapy in Myeloma: A New Era of Early Intervention

At SOHO 2025, Dr Noopur Raje will present a cutting-edge overview of CAR T-cell therapy in multiple myeloma, highlighting long-term efficacy data, novel targets like GPRC5D, emerging dual-targeting and in vivo CAR strategies, and the evolving role of CAR T earlier in the treatment paradigm as a potential path to functional cure.

Noopur S. Raje, MD: My name is Noopur Raje. I am the director for the Center for Multiple Myeloma at the MGH Cancer Center in Boston, and I'm also a professor of medicine at Harvard Medical School.

Can you provide an overview of your session at SOHO 2025?

Dr Raje: I'm excited to be at SOHO 2025. I am going to be giving an overview of chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma. We have come a long way, and we have a lot of exciting data that are going to be upcoming in the near future. My hope is that I try and go over all of this information. I'm going to start out by giving a little bit of background on what we already have available.

We have 2 CAR T-cell products that are approved in the context of multiple myeloma. We have cilta-cel and ide-cel, and they've already moved earlier in lines of treatment for multiple myeloma. For example, cilta-cel is available after just 1 prior line of treatment, and ide-cel can be used after 2 prior lines of treatment. It's really quite remarkable in terms of the progress we've made with CAR T-cell therapy. I am going to touch on the efficacy of these CAR products and look at the benefits of a one-time treatment with durable progression-free survival and durability of remissions.

I am going to touch on a little bit of data from the American Society of Clinical Oncology (ASCO) and the European Hematology Association (EHA), which have recently been published and presented, and mainly talk about the long-term outcomes of some of these CAR T-cell products.

How have the most recent clinical trials shaped our understanding of durability and safety in CAR T-cell therapy?

Dr Raje: I've just talked about the ones which are approved drug products. What we now know, based on long-term follow-up presented at ASCO—for example, with cilta-cel—is that beyond 5-years of follow-up, we have 30% of patients who are without any evidence of disease.

Those are the patients that I would dare to say that we have probably cured because, remember, these patients were receiving these treatments at the back end of their treatment, so they'd seen just about every treatment for multiple myeloma. Then we went in and gave them cilta-cel, and they have continued to remain in remission without having to be on any other treatment for more than 5 years. That is, in essence, our definition of functional cure in myeloma. We've come a long way.

I am also going to discuss some of the newer treatment approaches that we have with CAR T-cell therapy. Yes, we've got them earlier in the lines of treatment, but we are also thinking about using these immunotherapeutic approaches as early as in the upfront setting, as you will hear about in the CARTITUDE-5 and CARTITUDE-6 trials. Those, hopefully, will have mature data in them in the next couple of years.

There are some other novel targets that I will be referring to as well. We have GPRC5D, which we all know is a good targeted antigen expressed on multiple myeloma cells. There are data with a drug product called arlo-cel. I will be discussing this. This is right now in phase 2 and phase 3 trials, wherein we are seeing high response rates in excess of about 80% to 90%. The durability of response with a one-time treatment is also quite remarkable, about 18 to 19 months in this patient population.

There are other newer drug products that I will refer to. One of them is the anito-cel drug product, which is also in phase 3 clinical testing with the iMMagine-3 trial. There is also the dual-targeting CAR T-cell therapy, which targets not just BCMA but CD19 as well, and is being developed by AstraZeneca. We are going to be a part of the phase 2 studies with this drug product.

There are exciting data with CAR T-cell therapy going forward—not just with the old stuff, which is ide-cell and cilta-cel. We also have newer drug products, and we will have a dual-targeting CAR—not just targeting each of these antigens separately, GPCR5D and BCMA, but they're going to be targeted in concert with a dual-targeting CAR T-cell therapy, and that is in early clinical development as well.

Finally, I am going to touch on what the future is going to look like because, when we talk about CAR T-cell therapies, a lot of us worry about access to CAR T-cell therapy and also this waiting period of getting the CAR, getting those lymphocytes, manufacturing the CARs, and waiting for 4 to 6 weeks. Do people have the luxury of waiting before we give them the CAR product? Most recently, there's a small case series on an in vivo CAR, where they give the viral vector and actually create CARs in the person's body. This is also a CAR directed against BCMA, and at least the preliminary data in the first 4 patients looks really exciting and will be a game-changer for the future.

With CAR T now being considered earlier in the treatment paradigm, how do you envision its integration into the standard of care?

Dr Raje: Having the drug approvals early for CAR T-cell therapies is absolutely critical, and I do think it's going to change how we use these drug products. Being refractory to everything and [using CAR T-cell therapy] after 4 lines of treatment is really not a realistic way of treating our patients, specifically given that the paradigm for upfront treatment of patients with multiple myeloma has already changed. We are already using quadruplets in the upfront setting—an anti-CD38 monoclonal antibody—in the majority of patients. It's being used at the time of diagnosis and by the time they come to their first relapse, they've been exposed to at least 4 drugs already and they're refractory to at least 2 of those 4 drugs.

Getting the indication earlier is just a normal shift in the treatment paradigm. It's a welcome shift in paradigm. I do think this is going to influence practice wherein we are going to reach out for CAR T-cell therapies earlier. That should be the practice because if you do CAR T-cell therapy early, you have to worry less about the kind of bridging therapy and you have to worry less about the amount of disease burden, which we know are negative prognostic indicators when it comes to outcomes with CAR T-cells.

Is there anything else you hope that audiences will take away from your session?

Dr Raje: I hope that I can instill in them the excitement we have around CAR T-cell therapies, even though they're more designer-specific. Having the in vivo CARs in the making now is really a new, exciting paradigm in the treatment of patients with myeloma with these cell therapy products.

The biggest takeaway, for me—for the treating community hematologist/oncologist—is just that it's never too early to refer patients for CAR T-cell therapy because it does require a little bit of logistical groundwork to put the building blocks in place for getting to the CAR T-cell therapy.

The earlier you refer, the better. You've already seen that the indications for early CAR T-cell therapies are available, and the labels have changed, the REMS label has changed, and that should allow the easier referral for all physicians to a CAR T-cell center. The earlier you do it, the better the outcomes for our patients.