Oncologists Discuss CAR T Logistics and Bridging in Relapsed DLBCL

Chimeric antigen receptor T-cell (CAR T) therapy has transformed the treatment landscape for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), but optimizing patient selection, bridging therapy, and treatment logistics remains an important consideration in clinical practice.

During a live Case-Based Roundtable event with oncologists in Bernardsville, New Jersey, Lori Leslie, MD, director of the Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs at Hackensack Meridian Health John Theurer Cancer Center and assistant professor at Hackensack Meridian School of Medicine, discussed evolving considerations for CAR T therapy in second-line DLBCL, including the impact of recent changes to the risk evaluation and mitigation strategies (REMS) program, strategies for bridging therapy, and practical factors that influence candidacy and treatment selection.

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This is part 2 of a 2-part series. Read part 1.

Targeted Oncology^TM: How have changes to the REMS program affected patient access and logistics of treatment delivery?

Lori Leslie, MD: People may or may not be aware that the REMS program associated with CAR T was removed,¹ so that did change some of the required infrastructure. When there was a REMS program, you had to not [only] teach the oncologists and the cancer center; it [also] had to be all the emergency room doctors, intensive care unit doctors, pulmonologists, cardiologists, neurologists—anyone that may be encountering these CAR T patients had to be trained on that, which logistically was doable, but kind of a barrier to overcome. So now that's been reduced; it became that you didn't have to stay 4 weeks anymore; now it's 2 weeks. You used to not be able to drive for 8 weeks, now it's 4 weeks or the provider's decision. That 8-week no-driving strict restriction was a barrier for some of our patients, so I know that that was helpful.

CASE SUMMARY

• A 55-year-old man presents with progressive fatigue, abdominal discomfort, early satiety, and 10-lb unintentional weight loss over last 2 to3 months.
  • Reports intermittent night sweats and low-grade fevers
• Physical exam: Palpable cervical and abdominal fullness
• CT/PET-CT:
  • Diffuse lymphadenopathy above and below diaphragm
  • Bulky mediastinal mass (11.5 cm)
  • Multiple extranodal sites (gastric and small bowel involvement)
• Labs: Elevated lactate dehydrogenase; normal complete blood count
• Lymph node biopsy:DLBCL, nongerminal B-cell (GCB) subtype
• Bone marrow biopsy: Negative
• Immunohistochemistry: CD20+, BCL2+, MYC+, Ki-67 ~85%
• Fluorescent in situ hybridization: negative for translocations involving MYC, BCL2, BCL6
• Staging:
  • Ann Arbor: Stage IV disease
  • International Prognostic Index: 3 (high-intermediate risk)
• Initiated polatuzumab vedotin (Polivy)-rituximab (Rituxan)-cyclophosphamide-doxorubicin-prednisone (Pola-R-CHP) for 6 cycles
• Interim PET (after 3 cycles): Partial response (Deauville 4)
• End-of-treatment PET: Residual mediastinal uptake (Deauville 4)
• After 3 months, the patient begins to report recurrent fatigue and abdominal discomfort.
• Repeat PET-CT:
  • Persistent mediastinal mass with increased uptake
  • New abdominal lymphadenopathy
  • Deauville 5
• Patient is otherwise fit (ECOG performance status 1) and motivated for further treatment.

How are you thinking about bridging therapy for patients awaiting CAR T therapy?

I think there are a lot of nuances to bridging, and I don't think any of us really know the best thing to do because our treatment landscape is changing so fast. We used to use a lot of polatuzumab vedotin-based therapy for bridging, but now Pola-R-CHP is a common frontline regimen, particularly for patients like this one that have non-GCB LBCL, so this patient just got polatuzumab. How much is that going to be helpful in bridging? Bispecifics…now we have studies looking at bispecifics in frontline, so it's not going to be too long before we're seeing patients relapsing within a year when frontline therapy also included bispecifics, so I think it's such a rapidly evolving landscape. I agree that it's very patient-dependent.

What options do the NCCN guidelines dictate for second-line treatment of DLBCL for CAR T candidates?

The second-line CAR T products mentioned are axicabtagene autoleucel [axi-cel; Yescarta] and lisocabtagene maraleucel [liso-cel; Breyanzi], and then there are 2 different types of bridging. There's the holding therapy, which is before the CAR T gets collected, and then there's true bridging, which is once they're collected, while they're awaiting manufacturing and infusion.

There are some nuances in what we consider in those 2 different times, because what you give as holding therapy prepheresis will impact the T cells that you are taking out to use for CAR T manufacturing. What you use postapheresis, assuming the product is successful and doesn't need to be collected again, will impact the patient's microenvironment and what's going on at the time of CAR T infusion, but it will not impact those cells that were already removed. The general recommendation, for example, is to avoid things like bendamustine that can cause prolonged lymphopenia. There are data across different lymphoma subtypes that show bendamustine—particularly in follicular lymphoma, where we use bendamustine more—closer to CAR T is associated with poor outcomes, particularly within a year or even two.² So, as holding therapy, it's recommended to specifically avoid bendamustine. It's also generally recommended to try to avoid during bridging, though it is listed here as an option in kind of select situations to give polatuzumab-rituximab with the bendamustine. Our practice is just not to do that, but it is certainly a reasonable choice if that's the best option for the patient; we’re just really trying not to do that before collection.

Radiation therapy is listed, and I think there are more and more data about that as a bridge to CAR T, especially in patients that have more isolated relapse. That's a tool we use a lot. Sometimes we use it with a CD20 antibody or some other systemic therapy as well. But I think radiation therapy is somewhat of an underutilized bridge, probably because logistically it's a little more challenging than giving a patient a cycle of something, having them go to radiation daily, especially if they're not feeling great. But I think that's a nice option for some of those patients that are chemotherapy-refractory and don't need a long-term response because CAR T is the goal; you just need something to palliate and control while you await the manufacturing. There's a lot of other chemotherapy-based regimens—gemcitabine, platinum-based therapies—which all can be used again. Someone who just has primary refractory disease probably won't respond long-term. They can have a transient response to control without negatively impacting the T cells too significantly.

How do you rank the NCCN-listed treatment options for CAR T candidates, and how do you determine noncandidates?

It's very patient-specific. For someone who just got polatuzumab, if it's only been 3 months, we kind of hesitate to do that. But it's not a “never,” because again, we're just trying to control [the disease] a little bit to bridge them. We do a lot of radiation to bulky sites or symptomatic sites; I think that's a great bridge. If someone has not had polatuzumab, we typically do polatuzumab with rituximab. We have used lenalidomide [Revlimid], but not as much. I personally haven't come across using ibrutinib [Imbruvica]. We've used lenalidomide with ibrutinib in one patient I can think of that had a concern for central nervous system [CNS] disease at the time. For other patients that have CNS disease, we've used high-dose methotrexate to help control that while they're waiting as part of the bridging… We have used bispecifics too, but mostly in that situation where maybe the patient couldn't get a CAR T and [were an] uninsured or underinsured patient; we had to go through the process of trying to get free product and there was a delay.

If they're really relapsing quickly, I do think that's the place where we say they might not be a CAR T candidate just because they can't get there fast enough. We've done a rapid ramp-up of bispecific if they're chemotherapy- and polatuzumab-refractory. Or even sometimes it's really hard to get the oral agents, or the patients maybe can't swallow very well because they're so sick... So if it's multifocal, that's a place where we would go to the noncandidate for CAR T, and then hopefully bring them back.

DISCLOSURES: Leslie previously reported consulting/advisory roles with, travel support from, speakers bureau roles with or other relationships with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Eli Lilly, Epizyme, Evolveimmune, Genmab, Janssen, Karyopharm Therapeutics, Kite/Gilead, Merck, Pharmacyclics, Roche/Genentech, Seagen, and TG Therapeutics.

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REFERENCES

1. FDA eliminates Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor CAR T cell Immunotherapies. News release. US FDA. June 27, 2025. Accessed August 6, 2026. https://tinyurl.com/bp5pxxks

2. DeCicco D, Nethagani S, Waris S, et al. Impact of Prior Bendamustine Exposure on Chimeric Antigen Receptor T-Cell Therapy Outcomes in Follicular Lymphoma. Transplant Cell Ther. Published online August 2026. doi:10.1016/j.jtct.2026.07.039