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Case Challenges CAR T Lymphoma
Case Challenges: Expert Insights on CAR T-Cell Therapy and Adverse Event Management in B-Cell Lymphoma

Released: February 25, 2026

Jeremy S. Abramson
Jeremy S. Abramson, MD, MMSc
Stephen M. Ansell
Stephen M. Ansell, MD, PhD
David G. Maloney
David G. Maloney, MD, PhD
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Key Takeaways
  • For primary refractory DLBCL and high-risk relapsed/refractory FL, experts prefer treatment with CAR T-cell therapy.
  • Progressive neurologic toxicity following CRS typically requires escalation of steroids, introduction of anakinra, and multidisciplinary management and robust neurologic workup.

CAR T-cell therapy is an evolving and expanding field for treatment of B-cell lymphomas with new indications for currently FDA-approved CAR T-cell products and development of many novel agents. Jeremy S. Abramson, MD, MMSc; Stephen M. Ansell, MD, PhD; and David G. Maloney, MD, PhD, recently presented a Master Class satellite symposium at the 2025 American Society of Hematology (ASH) Annual Meeting and an encore webinar with the latest data from the meeting.  In this commentary, the faculty offer their approaches to 3 patient cases and insights from in-depth discussions with the audience at the ASH 2025 symposium.

Master Class Case: Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
A 74-year-old woman with DLBCL not otherwise specified, with a germinal center B-cell subtype and no MYC rearrangement, received the R-CHOP regimen as frontline therapy. An interim PET/CT scan after 3 cycles shows a mixed response, with persistent disease and new areas of progressive sites both above and below the diaphragm, raising concern for early primary refractory disease. A biopsy confirms primary refractory DLBCL. Clinically, she has tolerated treatment well and feels well, with normal marrow and organ function and a modestly elevated LDH level of 255 IU/L (upper limit of normal: 212 IU/L).

What therapy would you recommend next, and would you use bridging therapy?

David G. Maloney, MD, PhD: It can be challenging to decide the best approach to this case, whether to intervene with more bridging therapy or to go straight to CAR T-cell therapy. Based on the results of the ZUMA-7 and TRANSFORM trials, I would favor anti-CD19 CAR T-cell therapy for this 74-year-old patient. My approach would be to try to immediately harvest lymphocytes by apheresis. I would favor using lisocabtagene maraleucel (liso-cel) given its favorable tolerability compared to axicabtagene ciloleucel (axi-cel) for DLBCL and due to the patient’s age. However, I have certainly used axi-cell for older patients who have been able to tolerate it, although with more toxicity.

For bridging therapy, I would use polatuzumab vedotin with rituximab and omit bendamustine due to its T-cell toxic effects. If I felt we needed a more aggressive approach, I might consider 1 cycle of a gemcitabine-based regimen, like gemcitabine with carboplatin and dexamethasone, before CAR T-cell infusion.

Stephen M. Ansell, MD, PhD: The consensus among the ASH satellite symposium attendees was to proceed with CAR T-cell therapy for this patient. Product selection (axi-cel vs liso-cel) is a balance of access and turnaround time, as well as the patient’s fitness, but either product would be appropriate in this case. Among our international audience, there was discussion about a variety of bridging therapy options including bispecific antibodies (BsAbs) and chemotherapy, and there was enthusiasm for clinical trials.

Jeremy S. Abramson, MD, MMSc: This was a real patient of mine who was bridged with a single-cycle polatuzumab vedotin/rituximab and did very well. Her palpable adenopathy decreased and LDH levels decreased as well. She was treated with liso-cel and had no cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS). She achieved a complete remission that continues to this day more than 1 year later.

Master Class Case: High-Risk Relapsed/Refractory Follicular Lymphoma (FL)
A 61-year-old man was diagnosed with FL 3 years ago after presenting with widespread adenopathy and a high-risk FLIPI score. He received first-line bendamustine/rituximab (BR) for 6 cycles and achieved a partial response, but he developed progressive adenopathy 6 months later. He was subsequently treated with R-CHOP and achieved a complete response but developed progressive adenopathy again 1 year later.

Given this patient’s relapsed/refractory FL, what treatment would you consider now? For example, salvage chemotherapy, a BsAb (eg, mosunetuzumab, epcoritamab), CD-19 directed therapies (eg, tafasitamab, loncastuximab tesirine), or referral for CAR T-cell therapy?

Jeremy S. Abramson, MD, MMSc: I would consider this patient to have very high–risk FL. Most patients have a lengthy response to initial treatment and, if they relapse, a lengthy response to their second-line treatment. This patient had a very brief response to upfront chemoimmunotherapy and then a fairly brief response to second-line therapy with R-CHOP with a relapse only 1 year later. So, for third-line treatment of a high-risk patient like this, I would be deciding between a BsAb like mosunetuzumab or a CAR T-cell therapy. Complete response rates and progression-free survival are generally better for CAR T-cells than BsAbs, although outcomes are favorable for both options. However, for this patient with very resistant disease, I would prioritize the most definitive therapy possible, which I consider to be CAR T-cell therapy. As an alternative, for a patient with a short response to frontline therapy but a lengthy response to second line therapy, I more often treat with a BsAb.

Of note, this patient received bendamustine as frontline therapy which affects T-cell health, but with approximately 1.5 years since exposure to that treatment, they likely have adequate T-cell health and CAR T-cell therapy would still be appropriate.

Stephen M. Ansell, MD, PhD: Regarding some of the other treatment options, I would be concerned about affecting CD19 expression with an anti-CD19 agent prior to CAR T-cells in this type of patient. I may be less concerned about this for patients with lengthy remission histories who have more treatment options. In addition, a time-limited therapy with minimal time on treatment can be very desirable for patients of a young age like this one.

David G. Maloney, MD, PhD: The ASH 2025 audience mostly preferred CAR T-cell therapy in this case. The patient is young and fit, and the goal of treatment for a high-risk subset of patients with disease progression within 24 months (POD24) is a durable response. There was not a strong preference between CAR T-cell products among our US-based audience members. Among the international audience, treatment preference depended on what is available in their location and patient preference. In some countries, it can take months to secure approval for CAR T-cell therapy, which is the preferred treatment, so BsAbs were seen as appropriate treatment options in this case.

Master Class Case: Managing Neurologic Toxicity Following CRS
A 66-year-old man with relapsed mantle cell lymphoma receives brexucabtagene autoleucel after frontline BR and second-line zanubrutinib. On Day +2, he develops a 102°F fever and hypotension that is responsive to fluid boluses. He is treated with tocilizumab and dexamethasone which resolves his CRS. Three days later, he develops confusion with word-finding difficulty and aphasia. How would you treat this patient’s symptoms? If his neurologic symptoms progress (eg, somnolence or difficulty with activities of daily living), how would you escalate management?

David G. Maloney, MD, PhD: These symptoms would be consistent with grade 3 or higher neurologic toxicity, so I would start him back on dexamethasone, assuming it had been stopped. I would also be prepared to quickly start anakinra if his neurologic symptoms continued to worsen. Intravenous anakinra would be preferred over subcutaneous

Stephen M. Ansell, MD, PhD: There were a variety of views discussed among the ASH audience focused on reintroducing steroids and considering high-dose steroids, like pulse-dose methylprednisolone, if neurologic symptoms worsened. Most would also have a low threshold for adding anakinra depending on the clinical situation. However, anakinra is not available in all countries, so steroids were the primary treatment of choice for many practitioners. Alternative options to mitigate neurologic symptoms could include using cyclophosphamide to ablate CAR T-cells or the use of intrathecal chemotherapy. The audience and faculty also discussed the importance of multidisciplinary care and having a robust neurologic workup performed with MRI and EEG as neurologic symptoms progress.

Jeremy S. Abramson, MD, MMSc: This case was also based on a real patient of mine who was treated as our faculty and audience suggested. With the onset of his neurologic symptoms, we resumed dexamethasone and after those symptoms progressed, the dexamethasone dose was increased and anakinra was added. These symptoms gradually abated over 10 days. Unfortunately, the patient was deconditioned and required discharge to inpatient rehab. This case is representative of how neurologic side effects of CAR T-cell therapy can be prolonged and don’t resolve as quickly as CRS with tocilizumab.

Your Thoughts
How would you approach these cases? In the comments below, leave your questions or interesting patient cases to the faculty for possible discussion and answers.

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In your practice, which patients with B-cell lymphomas have you referred for or treated with CAR T-cell therapy?

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