Earlier CAR T-Cell Therapy Use Highlights Sequencing and Access Considerations in Myeloma

Earlier use of CAR T-cell therapies and bispecific antibodies is reshaping treatment selection in relapsed or refractory multiple myeloma, making sequencing of T-cell–redirecting therapies, patient preferences, and access increasingly important considerations, according to Omar Castaneda Puglianini, MD.

In an interview with OncLive^®, Castaneda Puglianini discussed how earlier CAR T-cell therapy approvals have influenced referrals, factors that guide selection between CAR T-cell therapy and bispecific antibody–based regimens in the early relapse setting, and opportunities to improve access through community education. He also highlighted ongoing frontline studies, in vivo CAR T-cell approaches, and emerging targets that could further shape the treatment landscape.

Castaneda Puglianini is an associate member of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and an associate professor in the Department of Oncologic Sciences at the University of South Florida.

OncLive: How have CAR T-cell therapies been integrated into the early-relapse setting following the second-line approval of ciltacabtagene autoleucel (Carvykti; cilta-cel) and third-line approval of idecabtagene vicleucel (Abecma; ide-cel)?^1,2

Puglianini: The number of patients receiving CAR T-cell therapy in early lines has increased. As a personal experience, I would say a little bit over half of my patients now are coming early on as a CAR T-cell referral, usually after progressing on maintenance lenalidomide [Revlimid] post-transplant.

Why is it important to have T-cell–redirecting therapies available earlier in the treatment paradigm?

T-cell–redirecting therapies like bispecific antibodies and CAR T-cell therapies are a milestone for myeloma therapy. It does make sense to continue to bring those therapies earlier in the patient's journey because you want to have your most efficacious therapies available. That's what has changed myeloma outcomes the way we see it, from having single agents, dual agents, triplets, and quadruplets—therapies that initially were approved in the relapsed/refractory setting, and right now, we are using all of them up-front.

Having CAR T-cell therapy as [early as the] second line and also having bispecifics in the second line with the teclistamab-cqyv [Tecvayli] and daratumumab [Darzalex] combination, that's very important.³ It's becoming a little bit trickier for us. How are we going to sequence? Who is the right patient for [CAR T-cell therapy vs a bispecific antibody]? The larger community oncology groups and the patients what are the preferences as well?

What factors guide treatment selection for a patient who could receive either CAR T-cell therapy or a bispecific antibody–based regimen?

Right now, the International Myeloma Working Group, in their sequencing guidelines, recommended that if a patient is eligible for both and both are readily available, they recommend CAR T-cell therapy first, followed by bispecifics.⁴

One of the reasons, aside from the preservation of T-cell fitness and avoiding unnecessary cumulative toxicity, was that there are data supporting the use of bispecific antibodies in subsequent lines following a prior BCMA-directed therapy, in this case, CAR T-cell therapy.

As well, we have data coming from cohort C [of the phase 2] CARTITUDE-2 trial [(NCT04133636) evaluating cilta-cel after prior non-cellular BCMA-directed therapy]. We have a bunch of real-world evidence studies that have shown how the efficacy of CAR T-cell therapy diminishes [in terms of] duration of response and complete response [rate] when the patients receive a prior T-cell–redirecting therapy before CAR T-cell therapy.

There is a nice review, point-of-view paper in Blood Advances that Doris Hansen, MD, [of Moffitt Cancer Center in Tampa, Florida,] and Luciano Costa, MD, [of the University of Alabama at Birmingham,] published recently, discussing how and in whom to use either bispecifics, CAR T-cell therapy, or, in general, BCMA-directed therapy.⁵ They had different ways of putting this together, looking at patient factors like age, frailty, comorbidities, toxicity, and treatment goals for the patient. They look at disease factors like tumor burden, tumor kinetics, whether there is extramedullary disease, high-risk cytogenetics, and the history of refractoriness to prior therapies.

Then they look into other factors: Does the patient have access to this therapy? Is there caregiver support? Is there a significant financial or logistical burden, or even geographic considerations where the patient is located? Based on those factors, then the therapy selection will go.

What advice do you give community oncologists about referring patients for CAR T-cell therapy?

We have a program where we go out and do education for our community partners, or our community partners invite us to discuss these topics in terms of bispecifics, CAR T-cell therapy, or even transplant.

The first thing is to know the data: What is the toxicity profile of each therapy? What is the efficacy of each? Also, what is the rationale behind the sequencing that we are pursuing at this time? Everything starts there. If the community oncologists are well informed about the data, then it's easier for them to transmit this information to patients.

There are community oncologists who prefer not to discuss this in full detail because they are not very comfortable with it, which is fine, but they already know where to send the patients. We are here in Florida. We are happy that we have about seven centers that provide CAR T-cell therapy for myeloma, so there are many places where the patients can go.

However, having said that, only a small fraction of patients with multiple myeloma are referred to academic centers or CAR T-cell centers. There is still a big gap in trying to have more patients, a bigger referral base, to the academic centers to further discuss therapy, as a way of optimizing management of myeloma.

How do you see CAR T-cell therapy evolving with new targets, in vivo approaches, and potential frontline strategies?

[In terms of] frontline strategies, we are participating in the [phase 3] CARTITUDE-6 study [(NCT05257083) evaluating cilta-cel in newly diagnosed patients], which is still ongoing, but we are going to continue to wait for results, probably for another couple of years. There is the [phase 3] CARTITUDE-5 trial [(NCT04923893) evaluating cilta-cel in transplant-ineligible, newly diagnosed multiple myeloma], where data are hopefully going to be presented sooner. Those two [trials] are going to make the case for up-front CAR T-cell therapy in transplant-eligible and -ineligible patients.

The field continues to evolve on that end. Even when you look at the newer targets or the dual-targeting CAR T-cell therapies, the natural space is moving these therapies early in lines of therapy.

In vivo CAR T cells are a great advancement. We are participating in a trial on these in vivo CAR T-cell therapies. We have treated our first patient. This is very promising, and it's still very early on. The technology is still only for patients with relapsed/refractory disease in phase 1 studies, so it's probably going to take some time. However, I have no doubt that, like everything that we have seen in myeloma, these therapies are going to continue to come to early lines, including up-front.

Then there are other targets [such as] GPRC5D with arlocabtagene autoleucel [arlo-cel], with some of the data looking promising. There are a lot of things coming that are going to make our work a little bit more difficult in terms of picking: Are we going to start with BCMA-directed therapy up-front? Are we going to save GPRC5D or other targets for down the road? What are we going to do with a quadruplet approach?

There is also therapy involving bispecific antibodies up-front, as part of induction therapy or as part of consolidation for those patients who are not minimal residual disease [MRD] negative after, let's say, transplant or induction therapy. There are many, many things coming right now. We have the CELMoDs also that are probably going to go on the same pathway in early lines.

We're going to have a lot of things. The way I see it is not as a competition of one therapy vs the other, but what therapy is the right one for the right patient in the right setting? Also, how do we use all those therapies to continue to prolong the survival of the patient?

References

1. Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at lease one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed October 12, 2026. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
2. US FDA approves Bristol Myers Squibb and 2seventy bio’s Abecma for triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. News release. Bristol Myers Squibb and 2seventy bio, Inc. April 4, 2024. Accessed October 12, 2026. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibb-and-2seventy-bios-Abecma-for-Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma-After-Two-Prior-Lines-of-Therapy/default.aspx
3. FDA grants third approval under the national priority voucher program. FDA. March 5, 2026. Accessed October 12, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program
4. Costa LJ, Banerjee R, Mian H, et al. International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma. Leukemia. 2025;39(3):543-554. doi:10.1038/s41375-024-02482-6
5. Hansen DK, Mateos MV, Costa LJ. Targeting BCMA in patients with relapsed/refractory multiple myeloma in 1 to 3 prior lines of therapy. Blood Adv. 2026;10(14):4931-4940. doi:10.1182/bloodadvances.2026019699