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CAR T Cell Therapy Updates
CAR T-Cell Therapy Updates: Key Highlights From Recent Conferences & Answers to Frequently Asked Questions

Released: September 30, 2025

Brad Kahl
Brad Kahl, MD
Noopur Raje
Noopur Raje, MD
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Key Takeaways
  • CAR T-cell therapies show durable remissions in lymphomas, with a potential first approval upcoming for marginal zone lymphoma (liso-cel).
  • 5-year update of cilta-cel shows that one third of patients with R/R MM remain progression free, potentially providing a “functional cure.”
  • New targets for CAR T-cell therapy, such as CD20 for lymphomas and GPRC5D and TACI for MM, may improve efficacy.
  • Allogeneic and in vivo CAR T-cell therapy may ease access to treatment by reducing CAR T-cell manufacturing times.

CAR T-cell therapies continue to transform the treatment landscape for leukemias, lymphomas, and multiple myeloma (MM). Recent major meetings, such as the American Society of Hematology and American Society of Clinical Oncology annual meetings, the European Hematology Associate Congress, and the International Conference on Malignant Lymphoma, presented pivotal clinical trial data, real-world outcomes, and emerging innovations that expand both the promise and complexity of these therapies. Although current approvals already demonstrate unprecedented durable responses in some patients, new and emerging CAR products and strategies aim to improve access, overcome resistance, and address unmet patient needs. In this commentary, Brad Kahl, MD, and Noopur Raje, MD, provide their thoughts on recent key updates along with answers to frequently asked questions related to the use of CAR T-cell therapy.

Recent Developments in Lymphomas

Brad Kahl, MD​:
I will begin with recent developments in large B-cell lymphoma. The pivotal randomized phase III ZUMA-7 trial demonstrated that axicabtagene ciloleucel was superior to standard of care (2-3 cycles of platinum-based chemoimmunotherapy) among patients with primary refractory disease, leading to its FDA approval in this setting. What is particularly reassuring is that real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry mirrored the ZUMA-7 results, showing similar efficacy and safety outcomes (1-year event-free survival: 54%; 1-year overall survival: 74%). These results suggest that the benefits observed in clinical trials are translating into everyday practice. Another recent presentation addressed whether CAR T-cell therapy or autologous hematopoietic stem cell transplantation (auto-HSCT) was more beneficial in patients with large B-cell lymphoma who achieve complete remission (CR) after salvage therapy. Data from both US investigators and the European Society for Bone and Marrow Transplantation (EBMT) indicate that auto-HSCT performs as well as CAR T-cell therapy in this scenario with no significant difference in overall survival, progression-free survival, response incidence, or nonrelapse mortality. These results support a potentially valuable strategy of first pursuing auto-HSCT and reserving CAR T-cell therapy for later if needed.

In follicular lymphoma, long-term follow-up data have been especially encouraging. In the single-arm phase II ELARA study of tisagenlecleucel, at 4 years, most patients were holding in remission, and among those who achieved CR, approximately 66% remained in CR, demonstrating a durable response. Similarly, in the phase II ZUMA-5 study of axicabtagene ciloleucel, at 5 years, nearly 60% of patients who achieved CR remained in CR. This level of durability after a 1-time therapy is impressive and reinforces my willingness to use CAR T-cell therapy for patients with relapsed/refractory (R/R) follicular lymphoma.

For marginal zone lymphoma, where CAR T-cell therapies have yet to be approved, data obtained from the marginal zone lymphoma cohort enrolled in the phase II TRANSCEND FL trial of lisocabtagene maraleucel (liso-cel) are promising. The overall response rate (ORR) in the efficacy-evaluable population was 95.5%, and the 2-year progression-free survival rate in the whole population was 85.7%, which supported liso-cel’s recent FDA priority review status and could support its accelerated approval in this setting. In mantle cell lymphoma, however, relapse after CAR T-cell therapy remains a major unmet need. Response rates to treatments like lenalidomide, rituximab, or immunochemotherapy following CAR T-cell failure are <25%, although bispecific antibodies show some early promise as a subsequent treatment option.

Finally, in chronic lymphocytic leukemia (CLL), liso-cel has been approved for patients who have received ≥2 prior lines of therapy including a BTK inhibitor and a BCL-2 inhibitor, but outcomes are more modest compared with other subtypes of lymphoma. Only approximately 20% of patients with CLL in the phase I/II TRANSCEND CLL 004 trial achieved CR, although for those who did, remission could last for 4 years or longer. Taken together, these updates highlight remarkable advances in some settings while underscoring critical gaps where new strategies are still urgently needed.

Recent Developments in MM

 Noopur Raje, MD:
Currently, there are 2 FDA-approved CAR T-cell therapies for R/R MM, both of which target BCMA: idecabtagene vicleucel​ (ide-cel) and ciltacabtagene autoleucel ​(cilta-cel). Ide-cel is approved after ≥2 prior lines of therapy, including an immunomodulatory agent (IMiD), proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody, whereas cilta-cel is approved after ≥1 prior line of therapy, including a PI and an IMiD, and refractory to lenalidomide. At the 2025 American Society for Clinical Oncology meeting, the most striking update came from the phase II CARTITUDE-1 trial of cilta-cel. After more than 5 years of follow-up, approximately one third of heavily pretreated patients remain progression free without additional therapy. This outcome suggests the possibility of a functional cure for some patients—an unprecedented outcome in MM. Both ide-cel and cilta-cel continue to demonstrate remission durations of more than 2 years in most patients, and I believe moving these treatments earlier in the disease course will yield even better outcomes.

Beyond these agents, several new CAR T-cell therapies are in development. Anitocabtagene autoleucel (anito-cel), another BCMA-directed CAR product, has shown promising efficacy with an ORR of 97% and promising safety with the incidence of grade ≥3 cytokine-release syndrome of 1% in the phase II iMMagine-1 trial for R/R MM and is now in phase III testing.

Of importance, progress is not limited to BCMA-targeting CAR T-cell therapies. Arlocabtagene autoleucel (arlo-cel), which targets GPCR5D, delivered ORRs >85% and a median duration of response of 18 months in the first-in-human phase I study, even in patients previously exposed to BCMA-directed therapies. Arlo-cel continues to be evaluated in the actively recruiting phase II QUINTESSENTIAL and phase III QUINTESSENTIAL-2 trials. Other future approaches to CAR T-cell therapy for MM include dual-targeting constructs against BCMA and GPCR5D, as well as innovative designs like TriPRIL CAR T-cells, which target both BCMA and TACI (highly expressed on MM cells).

Although CAR T-cell therapies have revolutionized the field, it is important to remain mindful of associated toxicities. Acute toxicities like cytokine-release syndrome and neurotoxicity have been recognized for many years and have well-established management strategies. There are some long-term risks such as delayed neurotoxicity and secondary malignancies, but their incidence remains rare. Even in the face of these toxicities, the benefits for patients are profound and I see CAR T-cell therapy as a true game-changer in the treatment of MM.

Frequently Asked Questions

For patients with CLL who progressed on a BTK inhibitor and venetoclax, do you wait for them to progress on pirtobrutinib prior to collecting T-cells for the production of CAR T-cells?

Brad Kahl, MD​:
Pirtobrutinib has a good response rate—approximately 80%—in patients who are refractory to both a BTK inhibitor and a BCL-2 inhibitor. However, responses are not highly durable. If I have a young patient who I think is fit enough for CAR T-cell therapy, I plan on collecting T-cells as soon as possible after pirtobrutinib treatment. I also look at their quality of response to pirtobrutinib. If they appear to be approaching CR or very good partial response, I will probably keep the patient on pirtobrutinib for as long as possible.

Is anito-cel expected to work differently from other BCMA-targeting CAR T-cell therapies?

Noopur Raje, MD:
Although cilta-cel, ide-cel, and anito-cel all target BCMA, they work slightly differently. Anito-cel is manufactured to bind more tightly to BCMA than the other products. The binding site is smaller; therefore, tonic signaling may be affected. The high response rates could be because of the tight binding, and the durable responses could be because of the decrease in tonic signaling. However, this is just a hypothesis and needs to be tested with longer follow-up.

Any there any clinical trials with allogeneic CAR T-cells?

Brad Kahl, MD​:
Yes, allogeneic CAR T-cells are being studied in lymphoma. Early outcomes are promising, so I do believe there is a lot of potential. This approach would help alleviate the manufacturing time and delays. I expect that we will learn more about the potential of these allogeneic CAR T-cells in lymphoma in the next 2-3 years.

Noopur Raje, MD:
In MM, this approach is not as encouraging. The early allogeneic CAR T-cell data had high rates of infections because of the need for highly immunosuppressive treatments. However, there are promising in vivo CAR T-cell therapies that remove the manufacturing step to treatment by administering a viral vector or nanocarrier to modify T-cells within the body. This field is moving forward quickly, so we will have to see whether a safe allogeneic CAR T-cell therapy or an in vivo therapy is approved first.

Your Thoughts
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