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CAR T Updates Hematologic Malignancies
Practice-Changing Advances in CAR T-Cell Therapy Across Hematologic Malignancies

Released: January 02, 2026

Amrita Krishnan
Amrita Krishnan, MD, FACP
Krish Patel
Krish Patel, MD
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Key Takeaways
  • Removal of REMS requirements for CAR T-cell therapy may improve patient access to treatment.
  • Liso-cel has been FDA approved as the first CAR T-cell therapy indicated for marginal zone lymphoma.
  • Emerging dual-targeting, allogeneic, and rapid-manufacturing CAR T-cell platforms may further expand therapeutic impact.
  • A new boxed warning for cilta-cel warns healthcare professionals about immune effector cell–associated enterocolitis, a rare and delayed adverse event.

CAR T-cell therapy continues to evolve and transform the treatment landscape for lymphomas and multiple myeloma (MM) with a new FDA-approved indication for an existing agent, new agents in development, and recent regulatory decisions. Amrita Krishnan, MD, FACP and Krish Patel, MD recently presented a live webinar on pivotal CAR T-cell therapy trial updates, real-world data, and emerging CAR products reported at the summer and fall congresses of 2025, including the Society of Hematologic Oncology annual meeting. In this commentary, they summarize that key data, as well as some further developments presented at the 2025 American Society of Hematology (ASH) annual meeting.

FDA Eliminates REMS for CAR T-Cell Therapy
Krish Patel, MD: I would like to begin by highlighting the FDA’s elimination of the Risk Evaluation and Mitigation Strategy (REMS) requirements for CAR T-cell therapies. When CAR T-cell therapy was first introduced, the field was cautious about its unique toxicities of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Over time, however, standardized grading systems, clear treatment algorithms, and extensive real-world experience have fundamentally changed how we manage these events. This is now reflected in the removal of the REMS requirements, as well as decreased restrictions on driving and how long patients need to be near a healthcare facility. Of importance, this change reduces the administrative burden of administering CAR T-cell treatments and may meaningfully improve access and rates of referrals.

Recent Updates in Lymphoma
Krish Patel, MD: Turning to lymphoma, large B-cell lymphoma (LBCL) remains the disease setting where CAR T-cell therapy has most clearly redefined standard of care. In the second-line setting for patients with primary refractory disease or early relapse, both axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have demonstrated superiority over traditional salvage chemotherapy followed by autologous stem cell transplantation (ASCT). What has been especially reassuring is the consistency between clinical trial outcomes and real-world data. Analyses of patients in the CIBMTR registry treated with axi-cel or liso-cel in routine practice show response rates, event-free survival, and overall survival that closely mirror those seen in the phase III ZUMA-7 and TRANSFORM trials, even in patients who may not have been eligible for the pivotal trials. This tells us that the benefits of CAR T-cell therapy are not limited to carefully selected trial populations but extend to patients encountered in everyday clinical practice. In addition, these real-world data reflect similar safety with low rates of severe CRS and manageable ICANS, reinforcing confidence in outpatient and community-based CAR T programs.

Across other lymphoma types, there have been several updates to pivotal clinical trials. For instance, in follicular lymphoma (FL), multiple long-term follow-ups of the ELARA study of tisagenlecleucel, including a 5-year update at ASH 2025, show that patients who achieve complete response (CR) often experience sustained progression-free survival (PFS) well beyond 4 years (CR rate: 68%; median PFS: 53.2 months). Similarly, 5-year follow-up from the ZUMA-5 trial of axi-cel demonstrates durable CRs approaching 5 years in a substantial proportion of patients with relapsed/refractory (R/R) FL (CR rate: 79%; median duration of response [DoR]: 60 months) or R/R marginal zone lymphoma (MZL; CR rate: 65%; 60-month DoR: 60%). Shorter 3-year follow-up of liso-cel in the TRANSCEND FL study also demonstrated continued high rates of durable responses (CR rate: 94%; 36-month DoR: 70%). Although FL has long been considered incurable, these data suggest that CAR T-cell therapy may deliver something approaching a functional cure for selected patients, particularly those achieving deep initial responses.

We also have updated data in mantle cell lymphoma for the ZUMA-2 trial of brexucabtagene autoleucel (brexu-cel). Five-year outcomes for patients with previous ibrutinib or acalabrutinib treatment have demonstrated high overall response rate (ORR) (93%) and CR rate (29%). At ASH 2025, 2-year updated results of patients with no prior BTK inhibitor exposure showed high ORR (91%) and CR rate (79%) which were similarly high amongst high-risk subgroups including those with TP53 mutations and high Ki-67. This suggests CAR T-cell therapy may be an effective treatment option for these patients who are not well treated within the current treatment paradigm which usually involves chemoimmunotherapy or the use of BTK monotherapy.

Important practice-changing data in lymphoma have been the primary results of the MZL cohort of TRANSCEND FL which showed notably high ORR of 95.5% and CR rate of 62.1% in the overall population with durable disease control. Even higher response rates were observed in patients with PET-positive disease at baseline (ORR: 98.1%; CR rate: 91.1%). These results led to the recent FDA approval of liso-cel for patients with R/R MZL after 2 or more prior lines of systemic therapy, marking the first CAR T-cell therapy approved for MZL. This approval fills a long-standing unmet need for these patients who previously had limited effective treatment options.

New Directions in Lymphoma
Krish Patel, MD: Looking ahead, the field is rapidly evolving beyond single-antigen targeting with many dual-targeting CAR T-cell constructs under ongoing study, most commonly directed against CD19 and CD20. Agents such as prizloncabtagene autoleucel (JNJ-90014496), KITE-363, rondecabtagene autoleucel (Lyl314), and zamtocabtagene autoleucel are designed to overcome antigen escape and deepen responses with early clinical data in LBCL and diffuse large B-cell lymphoma reporting ORRs as high as 91%, CR rates often >70%, and favorable safety profiles of low-grade CRS and ICANS. In parallel, rapid manufacturing technologies like KITE-753 and rapcabtagene autoleucel aim to deliver treatment within days of leukapheresis rather than weeks, and allogenic agents like cemacabtagene ansegedleucel have shown potential as future off-the-shelf options. Among other novel approaches, these innovations represent the next phase of CAR T-cell therapy, focused on improving durability, accessibility, and scalability.

Recent Developments in MM
Amrita Krishnan, MD, FACP: Turning to MM, we currently have 2 CAR T-cell therapies FDA approved in the R/R setting, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel). Last year we saw the biggest step forward in the field with both agents being approved in earlier lines of therapy with ide-cel approved after 2 or more prior lines of therapy including an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody. Cilta-cel was approved in the second-line setting after 1 or more prior line of therapy including an immunomodulatory drug and a proteasome inhibitor for patients refractory to lenalidomide. In 2025, we’ve seen updated data for the pivotal phase I CARTITUDE-1 trial with approximately one third of patients continuing to maintain PFS more than 5 years after treatment. Further real-world data reflected similar efficacy and safety as the original trial despite a majority of patients in the real-world group not meeting the trial eligibility criteria of CARTITUDE-1.

As the field has matured, attention has increasingly turned to toxicity mitigation. One emerging development has been the study of prophylactic dexamethasone during the early postinfusion period. A small study suggested that this may control excessive lymphocyte expansion and reduce the risk of delayed neurologic toxicity without compromising efficacy. Many centers have now incorporated proactive corticosteroid strategies into routine practice, though the true benefit of this approach remains unknown.

A more recently acknowledged safety consideration is immune effector cell–associated enterocolitis (IEC-EC), which has now been added as a boxed warning for cilta-cel. Although rare (2.2% incidence after cilta-cel and 0.2% after ide-cel), this complication can be severe and often presents with late-onset, nonbloody diarrhea. Awareness is essential, particularly for community healthcare professionals who may see patients months after CAR T-cell therapy. Possible risk factors include high CAR-HEMATOTOX score, high serum ferritin levels, and alkylator-based treatment within 3 months of CAR T-cell infusion. Prompt evaluation of patients presenting with diarrhea to rule out infection and T-cell lymphoma of the gastrointestinal tract (also reported in patients with IEC-EC after CAR T-cell therapy), as well as involvement of gastroenterology and infectious disease specialists can be lifesaving. This new boxed warning reflects our growing understanding of delayed CAR T-cell toxicities and the importance of long-term vigilance following treatment.

New Directions in MM
Amrita Krishnan, MD, FACP: The field of myeloma often quickly pushes treatments to earlier lines of the therapy after first approval in later lines. This extends to CAR T-cell therapy, which is under study in the frontline setting to possibly take advantage of more robust T-cells and achieve cure. We are anxiously awaiting the results of 2 such trials that have completed accrual. The phase III CARTITUDE-5 trial (NCT04923893) is evaluating bortezomib, lenalidomide, and dexamethasone (VRd) with cilta-cel vs VRd followed by lenalidomide and dexamethasone maintenance for newly diagnosed patients who do not intend to have ASCT as initial therapy. The phase III CARTITUDE-6 study (NCT05257083) is examining quad induction therapy followed by cilta-cel consolidation treatment vs quad induction followed by ASCT consolidation with 2 years of lenalidomide maintenance in both arms.

Beyond currently approved therapies, the myeloma CAR T-cell pipeline is rapidly expanding with novel targets, novel constructs, and dual-targeting approaches. For instance, arlocabtagene autoleucel (arlo-cel) targets GPRC5D and has demonstrated impressive phase I activity (ORR: 91%; CR rate: 48%) even in patients previously treated with BCMA-directed therapies. Arlo-cel is now under phase III study vs standard-of-care in the R/R setting. Similarly, anitocabtagene autoleucel (anito-cel), evaluated in the iMMagine-1 study, has shown exceptionally high response rates (ORR: 96%; CR rate: 74%) with encouraging safety and no delayed neurotoxicity. Finally, GC012F is a CAR T-cell therapy targeting both BCMA and CD19 and simultaneously designed to achieve rapid manufacturing time. Phase I studies in R/R MM and newly diagnosed disease have reported exciting results with ORR and CR rates as high as 100% and 97% respectively.

Your Thoughts
How often do you refer patients to CAR T-cell therapy and what are the biggest barriers you face when considering referrals? Do you believe that the latest regulatory changes regarding CAR T-cell therapy or the emerging CAR T-cell technologies we’ve discussed may address these barriers? Share your experiences and thoughts by answering the polling question and leaving a comment below.

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With the discontinuation of REMS for CAR T-cell therapies, will you consider referring more patients for CAR T-cell therapy eligibility screening?

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