CAR T-Cell Therapies Present Superior Efficacy, Security in A number of Myeloma

Barry Paul, MD, believes cilta-cel, anito-cel, and arlo-cel are among the most promising CAR T-cell therapies within the a number of myeloma house.

At the 2025 National Immune Cell Effector Therapy (ICE-T) convention, CancerCommunity® spoke with Barry Paul, MD, following a presentation he delivered on latest advances in CAR T-cell therapies in a number of myeloma.¹ These new therapies have been in a position to elicit deep remissions, whereas additionally being a “one and done” infusion, lowering the time for remedy administration, and fewer toxicity skilled.

Paul particularly talked about ciltacabtagene autoleucel (cilta-cel; Carvykti), anitocabtagene autoleucel (anito-cel), and arlocabtagene autoleucel (arlo-cel), as 3 of the present CAR T-cell therapies that maintain essentially the most promise in a number of myeloma. Cilta-cel, for instance, lately demonstrated a median general survival (OS) of 60.7 months (95% CI, 41.9-not evaluable); anito-cel has proven low charges of toxicities coupled with excessive response charges; and arlo-cel, in keeping with Paul, has the potential to be as efficacious as talquetamab-tgvs (Talvey), with much less toxicity.²

He additionally famous that the session he was part of on the convention mentioned the correct method to sequence CAR T-cell remedy with bispecific antibodies, significantly in group settings the place oncologists could not have the ability to provide CAR T-cell remedy as an choice.

Ultimately, Paul, an assistant professor of most cancers drugs at Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, mentioned that each one sufferers must be given an choice to obtain CAR T-cell remedy.

CancerCommunity: What is the importance of CAR T-cell therapies?

CAR T-cell therapies are extremely essential for [patients with multiple] myeloma. What these do is enable us to focus on particular antigens which might be distinctive to plasma cells in such a method that they get into the deepest attainable remissions. What we all know is that the deeper the remission that we are able to put a affected person into, the longer that remission tends to final. This is a one-and-done infusion for sufferers. They don’t should proceed to come back again for extra a number of myeloma remedy, which is extremely useful for them. These sufferers are used to being handled for years and years, so giving them a vacation from chemotherapy is one thing they really take pleasure in.

What are the usual remedy choices for sufferers with a number of myeloma?

We have plenty of totally different choices for our sufferers. We attempt to derive the very best remedy for every particular affected person primarily based on their distinctive state of affairs, their distinctive [multiple] myeloma, and what different comorbidities they might or could not have. Traditionally, we’d provide a chemotherapy-based routine that may be a mixture of immunotherapies and chemotherapies that focus on each the [multiple] myeloma cells instantly, in addition to the immune microenvironment. CAR [T-cell therapy] is a special method to handle some of these sufferers in such a method that they don’t seem to be essentially getting chemotherapy, however they’re getting an immune-based focused remedy that assaults the [multiple] myeloma on the highest diploma.

What novel advances in CAR T-cell remedy maintain essentially the most promise?

I’m inspired by the more moderen knowledge that was revealed for cilta-cel with the 5-year follow-up, with…[the median] OS being 60 months, or 5 years. Plus, about 33% of sufferers had been nonetheless responding to cilta-cel, and nonetheless at an entire response 5 years after their infusion. This is the primary time in a very long time that these of us who work in a number of myeloma are speaking a few attainable treatment…which is extremely thrilling. It could be great to have the ability to inform a affected person that they’re cured. That’s a really encouraging discovering.

The anito-cel knowledge is provocative, with excessive response charges in sufferers with high-risk illness and extramedullary illness. [There are] decrease dangers of long-term toxicities than we had been seeing with cilta-cel. It can be attention-grabbing to see if that continues to bear itself out with extra follow-up.

Finally, [there are] the arlo-cel knowledge, with the GPRC5D CAR [T-cell therapy]. GPRC5D is an unbelievable antigen goal to be focusing on primarily based on the information for talquetamab, however the toxicity with talquetamab tends to be very difficult to handle. Arlo-cel has the potential to be simply as efficient, if no more so, than talquetamab with much less toxicity. Those could be those I’m most enthusiastic about.

What are the toxicity issues with a number of myeloma?

There are early toxicities and late toxicities, and with the early toxicities, we are attempting to be extra aggressive about managing to forestall these late toxicities from manifesting. To be honest, we don’t essentially know as a lot about easy methods to stop these late toxicities, however we are attempting to do increasingly issues to intervene early and sometimes, to forestall a few of these early toxicities from maybe predicting extra threat for these late toxicities. The early toxicities are issues like cytokine launch syndrome, or CRS, and immune effector cell-associated neurotoxicity syndrome, or ICANS. These are usually low-grade if they don’t seem to be intervened upon quickly. This is why you’ll need to have some of these issues achieved at an skilled middle that has plenty of expertise managing some of these [adverse] results and has the power to take action early, in order that these [adverse] results don’t begin to lengthen into extra severe problems.

What are the following steps for bettering CAR T-cell therapies?

New antigen targets could be a giant one. We are focusing on this stuff in such a method that they’re very efficient, but when sufferers, in some unspecified time in the future, lose that antigen goal, then utilizing totally different mechanisms to focus on the identical antigen goes to be futile. Having extra choices for sufferers who’re closely pretreated and will have misplaced that antigen or have that antigen mutated in a method that it’s not responding to remedy will surely be efficient. That could be useful.

Ways to assist lengthen the good thing about CAR T-cell therapies: maintenance-based methods and issues like that to assist CAR T broaden, and to forestall overexpansion, the place we’ve got important [adverse] results. Those alternatives are a terrific place to start out.

What had been among the takeaways from the symposium?

One of the large ones is the sequencing of [CAR T-cell therapies] with or with out bispecific antibodies. These [CAR T-cell therapies] and bispecific antibodies focusing on BCMA share the identical goal, so the query could be, “What’s the best way to target these things? Is it to do a CAR [T-cell therapy] first or a bispecific first?”

In the group setting, the place loads of practitioners are snug providing a bispecific antibody however can’t do CAR T-cell remedy, are they doing a disservice in the event that they…provide these sufferers a bispecific with out having them evaluated for CAR [T-cell therapy], first? My particular thought course of on that is that there’s knowledge from the [phase 2 CARTITUDE-2 trial (NCT04133636)] and a few others that counsel that if a affected person has responded to a CAR T-cell remedy for no less than 6 months, they’ve an honest likelihood of getting a superb response to a bispecific antibody. The converse of that, if a affected person has had a bispecific antibody they usually had been handled till development, after which they had been challenged with a CAR [T-cell therapy], there’s much less efficacy in that house. I do imagine that each affected person must be provided a CAR [T-cell therapy] earlier than they’re provided a bispecific, with some uncommon exceptions for sufferers who’re frail or maybe have important comorbidities or don’t have entry to a CAR T-cell remedy middle.

What do you hope others take away from this dialog?

Everyone deserves entry to a CAR [T-cell therapy]. Send your sufferers to a specialty middle that has CAR [T-cell therapy] availability so we are able to consider these sufferers and actually decide if there’s a CAR [T-cell therapy] choice for them. For most sufferers, the reply to that can be sure, and most sufferers will do properly with it, not simply from a tolerability perspective, however from an efficacy perspective as properly. Those are definitely what sufferers are searching for. The different takeaway level is that the toxicities are manageable; that they’re there, however they’re manageable as we acquire extra expertise. That shouldn’t be a barrier for sufferers to get CAR T-cell remedy.

Reference

1. Paul B. Advances in CAR-T remedy for myeloma. Presented at: 2025 Immune Cell Effector Therapy Symposium; July 26, 2025; Orlando, FL.
2. Jagannath S, Martin TG, Lin Y, et al. Long-term (≥5-Year) remission and survival after remedy with ciltacabtagene autoleucel in CARTITUDE-1 sufferers with relapsed/refractory a number of myeloma. J Clin Oncol. Published on-line June 3, 2025. doi:10.1200/JCO-25-00760