Weighing Bispecific Antibodies Against CAR T-Cell Therapy in Follicular Lymphoma

Bispecific antibodies and CAR T-cell therapy have both become effective treatment options for patients with relapsed/refractory follicular lymphoma, prompting ongoing debate over how to best select and sequence between them. CancerNetwork® spoke with Nikesh Shah, MD, hematologist-oncologist at Tampa General Hospital who specializes in hematologic malignancies, including aggressive lymphomas and acute lymphoblastic leukemia and assistant member at Tampa General Hospital Cancer Institute, following a debate on this topic with Carlos Silva Rondon, MD, assistant member in the Department of Malignant Hematology and Cellular Therapy at Moffitt Cancer Institute at Memorial Healthcare System/Memorial Cancer Institute in Pembroke Pines, Florida, held at the National Immune Cell Effector Therapy (ICE-T) Conference in Orlando, Florida.¹

Shah discussed his assigned position in favor of bispecific antibody therapy, the disease- and patient-specific factors that shape the choice between a bispecific and CAR T-cell therapy, as well as how he counsels patients through the trade-offs of a single CAR T infusion vs an ongoing bispecific regimen. In addition, he touched upon where community oncologists may misjudge a patient’s candidacy for either approach, what data could shift the current treatment paradigm, and his key takeaway from the debate.

CancerNetwork: What was the context for this debate centered on bispecific antibodies and CAR T-cell therapy in follicular lymphoma, and what was your position?

Shah: We had a really fun debate with Carlos Silva Rondon, MD, of Moffitt Cancer Center at Memorial Cancer Institute in South Florida, about the pros and cons of bispecific antibody therapy vs CAR T-cell therapy in patients with follicular lymphoma. We were assigned topics by the conference directors, and I was on the pro-bispecific antibody side. At the end of the day, there are a lot of pros and cons to both, and it is about having a conversation with the patient and knowing the patient in front of you to pick the best therapy.

How much does the generally indolent nature of follicular lymphoma change the decision-making process around choosing a lower-toxicity option like a bispecific vs committing to CAR T-cell therapy’s more intensive, higher-response approach?

You have to think about the disease, the trade-off of how aggressive it is, and what toxicities you and the patient in front of you are willing to accept. When we think about more aggressive hematologic malignancies, especially acute lymphoblastic leukemia or aggressive large cell lymphoma, we are more willing to accept a higher toxicity trade-off because we need to control the disease quickly. A lower-grade, more indolent follicular lymphoma calls for very different decision-making, so you have to understand the disease biology and the risk and pace of disease growth in the patient. Some patients with follicular lymphoma have aggressive, rapidly growing disease, and you are concerned they may be transforming to a large cell component. Others have slow-growing disease, and I do not necessarily need to commit them to the potential neurologic toxicity and other risks of CAR T-cell therapy when a bispecific antibody might be a great option.

How do you talk patients through the trade-off between a single CAR T infusion with a defined toxicity window vs an ongoing bispecific regimen with a different, more chronic risk profile?

I lay out the options: we have CAR T-cell therapy, a bispecific antibody or bispecific combination, or [different] options. We go through the logistics, the toxicities, and the outcomes, but you have to get a sense of the patient’s goals. Some people would much rather have a “one-and-done“ infusion and not need infusions again for, hopefully, a long time, whereas others would rather avoid potential hospitalization and a higher risk of [adverse] effects and instead come in weekly—or however often needed—for a bispecific antibody.

A lot of that also depends on where someone is in their stage of life. Younger patients who are in the workforce or have young children often say they would rather have a compressed timeline than be busy early on with CAR T-cell therapy, with hopefully a long treatment-free interval afterward. Older, retired patients do not necessarily mind coming in as often. The big thing I point out to people is that CAR T-cell therapy is a kind of “one-and-done” therapy, but there are still a lot of visits before and after it. There is a good time-toxicity study that looked at exactly this question, and it lines up with what we see in clinical practice: with CAR T-cell therapy, the time toxicity is pushed into the first 2 months and then levels off, whereas with bispecifics, it is a slower, steadier burden that is less intense but persists longer.²

Where do community oncologists most often get the decision between bispecifics and CAR T-cell therapy wrong, when a patient with follicular lymphoma could reasonably receive either modality?

There are a few important points. One is that physicians who do not often see patients receive CAR T-cell therapy tend to generalize it as a high-toxicity therapy, which can be true, but it is dependent on the disease, the product, and the patient’s comorbidities. Some CAR T-cell therapy products, especially in patients with a lower-grade disease burden, have manageable toxicities. I have found a gap where a physician may think a patient cannot receive CAR T-cell therapy because they are too sick or have too many comorbidities, then refer them for a bispecific instead; but when we have an in-depth conversation with the patient, they can turn out to be reasonable CAR T-cell therapy candidates if that is what makes sense for them.

The other piece is that this is a very nuanced conversation, and it takes time in front of the patient to work through the decision-making. The real pressures of community oncology make it hard to spend a long time with a patient, having an in-depth conversation when a clinic might have 40 patients that day. We try to build relationships with community physicians so that, even through a one-time telehealth visit with our lymphoma CAR T-cell therapy center, we can have that conversation with the patient. They may end up receiving a bispecific fully in the community or get referred to us for CAR T-cell therapy ramp-up and then continue maintenance closer to home. It is worth having that initial discussion because, in follicular lymphoma, the goal is sequencing therapies; it is a marathon, not a sprint.

What would change your mind about the current sequencing paradigm in relapsed/refractory follicular lymphoma?

Long-term follow-up is really what we need. For CAR T-cell therapy in follicular lymphoma, we have longer-term follow-up: [Dr Silva Rondon] showed 10-year follow-up data showing that the curve seems to level off, meaning we may be curing some patients with CAR T-cell therapy.³ We do not think about that as much in follicular lymphoma. We do not yet know [if that’s the case] for bispecifics in the relapsed/refractory setting, so long-term follow-up is one factor.

I am also excited for the next few years of second-line and frontline data in follicular lymphoma with bispecifics. That is where we are heading, and although we do not know what the future holds, I expect that in the next few years we will be leaning on bispecifics very early on, especially for patients [with high-risk disease].

What do you hope those in attendance took away from today’s debate?

The key point is that it is always better for the patient to have more options. Thankfully, we are now at a point in follicular lymphoma where we have multiple good options for patients. It is difficult for us as providers to have these detailed, nuanced conversations with so many options, but it is good for the patient to be able to select the therapy that makes the most sense for them, based on their goals and their specific situation.

References

1. Shah NN, Rondon CS. R/R follicular lymphoma- BsAbs or CAR T-cell therapy. Presented at the 2026 National ICE-T Conference; July 18, 2026; Orlando, FL.
2. Major A, Abbott D, Snyder J, et al. Comparison of real-world survival outcomes and time toxicity of CAR T-cell versus bispecific antibody therapies in relapsed/refractory follicular lymphoma: a multicenter cohort from 15 US academic institutions. Blood. 2025;148(suppl 1):1798. doi:10.1182/blood-2025-1798
3. Ruella M, Paruzzo L, Chong ER, et al. Ten-year outcomes after CAR T-cell therapy for B-cell lymphomas. N Engl J Med. 2026;394:2440-2448. doi:10.1056/NEJMoa2518035