Should Those with Non-Hodgkin Lymphoma Receive CAR T or Bispecifics?

For the 2025 Immune Cell Effector Therapy (ICE-T) Congress, CancerNetwork® hosted a panel discussion consisting of cellular therapy experts, during which they were prompted on whether CAR T-cell therapy or bispecific antibodies are optimal for patients with relapsed/refractory large B-cell lymphoma.

The panel included Forat G. Lufti, MD, assistant professor of Hematologic Malignancies and Cellular Therapeutics at Kansas University Medical Center; Nausheen Ahmed, MD, associate professor of Hematologic Malignancies and Cellular Therapeutics at Kansas University Medical Center; and Sayeef Mirza, MD, MPH, FACP, hematologist/oncologist at Moffitt Cancer Center.

The experts discussed which therapy they prefer if a patient is eligible for both, highlighting the factors that have the largest influence on their decisions. The factors ranged from disease burden and physical fitness to patient preferences.

Transcript:

Lufti: This is probably the most contentious question that everybody argues about. My bias, that is somewhat backed up, is if you’re eligible for both, and if you can get a patient CAR T, you should get them CAR T; the long-term data are there for CAR T. We have 3-year and maturing data for bispecifics, but we’re not completely convinced that this [treatment] is necessarily [curative]; obviously, it will be for a number of patients, but we have 5-year plus data on CAR T that has been a paradigm shift in the last 30 years.

The second thing is what data we do have because, obviously, a head-to-head [trial] is unlikely to occur [for] CAR T vs bispecifics. We have meta-analyses, and we have retrospective studies looking at [large B-cell lymphoma]. A recent meta-analysis that was published was favorable towards CAR T both in terms of response rates and in terms of long-term progression-free [survival] and overall survival. With that said, we’re taking more toxicity on with CAR T. The thing, though, is that the toxicity is up front. Bispecifics may have less toxicity upfront, but we still don’t necessarily know in the long term. When we think about non-relapse mortality, it’s most likely higher with CAR T, but it’s not insignificant in the bispecific population. Many of the registrational trials for bispecifics had non-relapse mortality predominantly due to infection—it’s approaching 5%. That’s not insignificant. Some is even higher than that. In general, if they’re eligible, and if I can choose either CAR T or bispecifics in large B-cell lymphoma, I’m going to choose CAR T.

Ahmed: In an academic center, the absolute right answer is going to be CAR T because of the survival benefit. The efficacy matters, and the fact that it’s a 1-time treatment and not an ongoing treatment…is an advantage to CAR T. In this day and age, the correct answer is to do CAR T first. I do see where access may be an issue, even if it’s medically advised—when I say access, I’m talking about if the caregiver is available. If the patient is able to relocate [with] all the logistical issues that come with it, does the patient want to come and travel a long distance? Those factors become important when a patient is 4 hours away and the physician has to make a decision about referring or not. The patient may have a bigger say about whether CAR T or bispecifics are going to be the right option for them. Maybe they both will not be available at that location. It’s a bigger question, more than just medically. What’s the right answer? Back to the same thing, I’d say we’re looking, medically, at [fitness] and the disease status of the patient. Then, physical fitness, frailty, patient preference—all those things come into play.

Mirza: I think the data are pretty convincing, and the complete response [CR] rates are a little bit higher for CAR T. With that being said, you’re comparing 2 different types of treatments. One is a 1-time infusion, and one is an indefinite treatment, or up to 2 years. When the patient is offered those 2 different options, you can tell where they’re going to go. But then again, I agree with Dr Ahmed that access, feasibility, and wherever they are in the community are concerns. Sometimes, a caregiver can accommodate 1 type of caregiving vs moving to a CAR T center and living with them for a couple of weeks. That requires much more from a caregiver, for example. All those things are factored in, but bispecific T-cell engagers [BiTEs] remain helpful and useful, and [they] are potentially pragmatic for some patients because they don’t have access to a CAR T….It’s important to have both therapies; how we sequence them and how we strategize them is a personalized approach. You [need to] look at the patient’s disease factors and decide how to get the patient where they need to go to get into remission or [to achieve] a durable response and try to prolong their life and their quality of life. All that is taken into account.

Ahmed: I wanted to add that I feel like educating patients about the curability aspect of CAR T may be important. Again, they are a key stakeholder in this decision. Similarly, [it is key to] educate the community [hematologist-oncologists] that refer the patients, and to have a low threshold to refer the patients. There may be some financial barriers or other things that, even in the tertiary center, we may be able to navigate through. Patients may not realize, for example, that there is support to help with relocation. There is support to help with many things, so that they don't have to foot all the bills themselves. We need to get that word across that there is help. That might be important.