Considerations for CAR T Therapy in R/R Large B-Cell Lymphoma

Chimeric antigen receptor (CAR) T-cell therapy continues to reshape the treatment landscape for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). During a live Case-Based Roundtable event in The Woodlands, Texas, Paolo Strati, MD, associate professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, reviewed evolving treatment strategies for patients with R/R LBCL, with a particular focus on the timing of CAR T therapy and the growing role of bispecific antibodies. The conversation also explored surveillance practices, emerging frontline therapies, and navigating practical barriers to CAR T access.

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This article is part 2 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

A 60-year-old man presented with fatigue, back pain, and lymphadenopathy.

• Past medical history: Well-controlled hypertension
• Physical exam: left posterior cervical node (1.5 cm); right anterior cervical node (2.5 cm); left supraclavicular node (2.0 cm)
• PET-CT: multiple enlarged mesenteric and retroperitoneal nodes, largest 5.3 x 3.1 cm
• Bone marrow biopsy:Negative
• Lymph node biopsy: confirmed DLBCL, nongerminal center B-cell, double-expresser lymphoma
• Normal complete blood count
• International Prognostic Index: high-intermediate risk; nongerminal center
  • Age ≥ 60 y, elevated lactate dehydrogenase (LDH), stage III or IV disease
  • ECOG performance status ≥ 2
  • >1 extra nodal site

Targeted Oncology: The patient was referred to the nearest transplant center for CAR T evaluation. When would you consider CAR T therapy for patients with R/R LBCL?

Paolo Strati, MD: The first [time] when you can start looking into CAR T is in the second line. We cannot yet utilize CAR in the front line, though this may change in the near future. There's an ongoing large, randomized phase 3 trial [NCT05605899] that is trying to look into CAR T in the front line for patients who have high-risk features like…those who have less than a [complete response; CR] in response to 2 cycles of chemotherapy.

For identifying patients with primary refractory disease early, what is your preferred frequency of imaging scans during frontline treatment and surveillance?

As for frequency of scans, I feel like, at least in my personal experience, in the first couple of years, there's more flexibility in doing scans more frequently. But then beyond the first 2 or 3 years, scans will not be allowed more frequently again. But as CAR T is available in the second line, I personally do scans every 2 cycles during the frontline treatment, and every 2 to 4 months the first year, every 6 months the second year. And once you get to the 12 months from the end of treatment, then you can be a little bit more flexible, but you don't want to miss that chance, understanding that the chance of being primary chemo-refractory is not very high; it's about 20% of patients, but it's not 0%.

How are the NCCN guidelines influencing the use of bispecific antibodies in the second-line setting?

One point that I want to make is that you will increasingly hear about the possibility of utilizing bispecifics in the second line in combination with chemotherapy. And this is based on a randomized trial…where a bispecific plus chemotherapy was compared with chemotherapy, and there was a survival benefit, but because there was underrepresentation of the US population, we did not get an FDA approval, though this may change. So as of today, we cannot really use bispecifics in the second line, even in combination with chemotherapy, but based on the NCCN guidelines, many of us do. And so we're finding ourselves in the situation where we're using, let's say, glofitamab [Columvi] plus gemcitabine and oxaliplatin or epcoritamab [Epkinly] plus gemcitabine and oxaliplatin as either a holding or a bridging treatment while we wait for either apheresis or CAR T-cell infusion, and patients achieve a CR and then we don't know what to do. If we're happy with a bispecific, should we still proceed with CAR? Personally, because it's a scenario that we are encountering increasingly in our practice, my take is that we do have 5-year follow up for CAR T and we do have a clear overall survival benefit for CAR, so we can make the statement the CAR can endure patients with LBCL. We can’t yet make the statement for bispecifics; maybe we will in about 2 years from today, once there is more mature follow up. So in my personal practice, if I'm using a bispecific in the second line as a holding or a bridging treatment and I'm able to achieve a CR, and the CAR T-cell product is ready, I will still go ahead and give the CAR, even if the patient is in CR.

How could emerging frontline CD19-targeted therapies affect the future role and feasibility of CAR T therapy in second-line LBCL?

There's been a press release recently showing a randomized trial [frontMIND; NCT04824092] comparing R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] and tafasitamab [Monjuvi] that was positive.¹ So most likely in 2026, tafasitamab, targeting CD19, will become a frontline treatment. And my big question is, once that happens, are we going to have too many CD19-negative patients in second line, and so CAR will not be feasible? The 2 randomized trials trying to bring bispecifics to the frontline are still in very early stages, so it will probably take 3 to 5 years before we get there, but they're coming. And so, [there’s a] very high chance that we will find ourselves in a situation where you're using a bispecific in frontline. I don't know if that is going to result in a higher rate of cure. Still, CAR T cells will be available in the second line. So, my big concern is more for once tafasitamab becomes a frontline option, how will that affect human decisions in the second line?

What resources are available to address the nonclinical barriers to CAR T therapy?

One thing that I usually recommend… there are some patient partner organizations like Lymphoma Research Foundation [LRF]. If you just put them in contact with your patient, they can point them to the right resources. The companies who own the [CAR T] products you have sometimes have access to small grants; they can use some funds. The patient partner organizations themselves can, and most likely when you do the referral to your social worker, that's what they're doing also; they're just sharing your patient resources…There will never be, of course, 100% coverage of the cost of CAR T or the logistics around CAR T, but for those who are in financial need, as I said, either the companies themselves or American Cancer Society will provide some degree of support.

Once the patient makes it to the academic center and they start having the conversation, we will connect them to our own social worker; they will connect them to the right resources. But I think that what we want to try to capture is what happens beforehand. Some patients don't even make it to the academic center because, out of concern for logistical barriers, didn't even want to go there for the first visit. So my suggestion would be, when you start having a conversation…if you receive any resistance from your patient because of nonclinical barriers, doing something as simple as making them aware of the LRF—and I'm saying this out of personal interest—they can very easily, at least, list for them what the options are, and they can make a decision whether, based on those, would be willing to have their first consultation.

We had this big meeting in Washington in September about CAR T access organized by the LRF, and we invited all the stakeholders, including companies. And there were so many resources that we were not aware of, and sometimes even your social workers may not be aware of, particularly working in community oncology. I do think that a very easy hub is the LRF; that would be my suggestion. There's a landline that a patient can utilize, and they have a very reliable list of every possible resource to be able to [overcome] all of these nonclinical barriers.

DISCLOSURES: Strati previously disclosed a consulting role with Hutchinson MedoPharma and Roche Genentech; memberships on a Board of Directors or advisory committee at Sobi, AstraZeneca Acerta Pharma, Kite Gilead, and ADC Therapeutics; and receipt of research funding from Sobi, AstraZeneca Acerta Pharma, Kite Gilead; ADC Therapeutics, and ALX Oncology.

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REFERENCES

1. Incyte Announces Positive Topline Results from Pivotal Study of Tafasitamab (Monjuvi®/Minjuvi®) as a First-line Treatment for Diffuse Large B-Cell Lymphoma. News release. Incyte. January 5, 2026. Accessed May 7, 2026. https://tinyurl.com/3kcd54h2