Choosing the optimal third-line therapeutic strategy for relapsed/refractory follicular lymphoma remains a complex clinical decision, as highlighted in a recent debate between Nikesh N. Shah, MD, and Carlos Silva Rondon, MD, at the 2026 National ICE-T Conference in Orlando. Both CAR T-cell therapy and bispecific antibodies are recommended options, but each carry distinct operational, biological, and toxicity profiles that require careful patient selection.
Shah initially noted that because follicular lymphoma is generally an indolent, low-grade malignancy, clinicians must carefully weigh toxicity trade-offs. For patients with a slow-growing disease pace, bispecific antibodies present an attractive alternative to the potential neurotoxicity associated with cellular therapy. Conversely, Silva Rondon advocated for CAR T-cell therapy in patients with rapidly growing disease or a high clinical suspicion of high-grade transformation into large B-cell lymphoma, as cell therapies may offer deep complete response rates and a defined, one-time treatment duration.
While continuous bispecific therapies can introduce long-term financial toxicity, advancements in modern CAR T-cell products have significantly improved the early mitigation of adverse effects, even enabling outpatient administration for select candidates. Ultimately, the choice depends on sequencing strategy, healthcare access, and the unique clinical and financial landscape of the patient.
Shah is a hematologist-oncologist at Tampa General Hospital who specializes in hematologic malignancies, including aggressive lymphomas and acute lymphoblastic leukemia. Silva Rondon is a hematologist, oncologist, and bone marrow transplant specialist at Moffitt Malignant Hematology and Cellular Therapy at Memorial Healthcare System/Memorial Cancer Institute in Pembroke Pines.
Transcript:
CancerNetwork®: What was the context for this debate centered around bispecific antibodies and CAR T-cell therapy in follicular lymphoma? What was your position on the matter and why?
Shah: We got to have a really fun debate with Carlos Silva, MD, down at Memorial [Healthcare System] in South Florida, talking about the pros and cons of bispecific antibody therapy vs CAR T-cell therapy in patients with follicular lymphoma. We got assigned topics by the conference directors, so I was on the pro-bispecific antibody side. But, at the end of the day, there are a lot of pros and cons to both, and it’s about having a conversation with the patient and knowing the patient in front of you to pick the best therapy.
Follicular lymphoma is generally a more indolent disease than the aggressive lymphomas you also treat. How much does that change the decision-making process around choosing a lower-toxicity option, like a bispecific, vs committing to CAR T’s more intensive, higher-response approach?
You have to think about the disease and the trade-off of how aggressive that disease is. What are the toxicities that you are willing to put up wit? Within the context of the patient sitting in front of you, and at the end of the day, what are they willing to put up with? When we think about our more aggressive [hematologic] malignancies, especially when we talk about [acute lymphoblastic leukemia] or really aggressive large B-cell lymphoma, we are okay with a little more trade-off because it’s a really [high-risk] disease that needs to be controlled quickly, so we are willing to accept slightly higher toxicity risk.
Whereas [with] a lower-grade, more indolent follicular lymphoma, your decision-making is very different. That’s why you really have to understand the disease biology, the risk, and pace of disease growth in the patient in front of you. Some of these [patients with] follicular lymphoma have really aggressive, rapidly growing disease, and you’re concerned they might have transformed to a large cell component, but some have really slow-growing disease where you don’t necessarily need to commit them to the potential neurological toxicity and things of CAR T-cell therapy when a bispecific antibody might be a great option.
What was the context for this debate centered around bispecifics and CAR T in this disease state? What was your position on the matter and why?
Rondon: Both therapies are currently recommended for relapsed/refractory lymphoma beyond 2 lines of therapy. The debate addresses the reality of the real world: who has access to CAR T-cell therapy, who has access to bispecific therapy, [and who] is the right candidate for one therapy? [Also,] understanding where the field is, how do we sequence them, how do we look at them, and what is the patient selection for that? I’ll be advocating [for] CAR T-cell therapy. I’m a cell therapy doctor, so I’m excited to talk about that.
What patient- or disease-specific factors like comorbidities, prior lines of therapy, pace of relapse, or concern for histologic transformation weigh most heavily in your sequencing decisions for treatment?
You highlight the most critical points about what to think when you have the patient in front of you and when you’re going to select therapy. Technically, if you have demonstrated that they have transformed, or there is a clinical suspicion for that, you think that the best and the most successful therapy—in this case, CAR T-cell therapy—will be the right choice for a patient. They will have a potentially higher overall response rate, complete response rate, and better progression-free survival, including in this case if there is a concern for large B-cell lymphoma.
Now, if we look at the patient, we also have to keep in mind the age of the patient—whether this patient is a young patient vs older. We have to keep in mind a one-time treatment vs long therapy, whether it’s in a combination of a bispecific, let’s say with [lenalidomide (Revlimid)] and a year of therapy, or mosunetuzumab [Lunsumio] for a dedicated [duration] vs epcoritamab [Epkinly] that is continuous. That also has some financial burden that might be not upfront like it is with CAR T, but long-term financial toxicity is also a matter to keep in mind.
As patient selection has improved as we’ve been performing CAR T-cell therapy for more years, we 1784665249 understand how to address toxicity and address it earlier. It depends also on the product because we have products that we can potentially [give] outpatient, such as [lisocabtagene maraleucel (liso-cel; Breyanzi)], and in this case, [tisagenlecleucel (Kymriah; tisa-cel)] and liso-cel toxicity is somehow close to bispecifics. With the experience that has been built over the years, and in the right setting, it is an opportunity to treat patients who have comorbidities or who are older without necessarily increasing the treatment-related mortality significantly.
