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Bridging to CART in MM ASH 2025
Expert Reflections on Bridging Therapy Before CAR T-Cell in MM: Key Updates From ASH 2025

Released: February 09, 2026

Krina K. Patel
Krina K. Patel, MD, MSc
Noopur Raje
Noopur Raje, MD
Surbhi Sidana
Surbhi Sidana, MD
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Key Takeaways
  • Response to bridging therapy before CAR T-cell therapy is a key indicator of safety, as achieving disease control (≥ PR) prior to infusion is associated with a more favorable CAR T-cell safety profile.
  • Nonresponse to bridging therapy and elevated peak absolute lymphocyte count were identified as potentially modifiable risk factors for CAR T-cell therapy–associated delayed neurotoxicity.
  • Individualizing bridging therapy and monitoring immune kinetics may enable proactive strategies to reduce toxicity and improve patient outcomes in R/R MM.

As CAR-T cell therapy becomes more widely adopted in relapsed/refractory (R/R) multiple myeloma (MM), we face an evolving challenge: how to deliver these therapies safely and predictably without compromising their deep and durable responses. Although both ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) have demonstrated impressive efficacy in real-world settings, 2 recent retrospective studies presented at ASH 2025 reveal important safety signals that should inform our clinical approach moving forward. Central to both is a clear message: Nonresponse to bridging therapy is a key modifiable risk factor for the safe administration of CAR T-cell therapy. In this commentary, leading experts in CAR T-cell therapy for MM, Krina K. Patel, MD, MSc; Surbhi Sidana, MD; and Noopur Raje, MD, share their insights into what these new data mean for bridging strategy selection and how optimizing response before infusion may improve CAR T-cell safety in real-world practice.

Bridging Response as Predictor of CAR T-Cell Therapy Toxicity

Noopur Raje, MD
Managing toxicity is one of the biggest hurdles to getting patients safely to and through CAR T-cell therapy in R/R MM. Now that ide-cel and cilta-cel are approved, it is more important than ever to understand what stands in the way of patients reaching these treatments safely. Bridging therapy is often needed during wait times, but how well it controls disease can directly affect safety after CAR T-cell therapy infusion. New data presented at ASH 2025 are helping us better understand how to use bridging therapy to support both the success and safety of CAR T-cell therapy.

Let’s start with data obtained from 2 large patient cohorts: one from the US MM Immunotherapy Consortium and another from a single-center analysis where it was seen that nonresponse to bridging therapy emerged as a key risk factor for CAR T-cell–related toxicities.

Surbhi Sidana, MD
In the US MM Immunotherapy Consortium analysis, investigators evaluated 761 patients treated with standard-of-care cilta-cel across 15 centers and found that response to bridging therapy strongly influenced CAR T-cell safety outcomes. Delayed neurotoxicity occurred in 10.0% of patients, with parkinsonism in 2.9%, and rates were significantly higher among those who did not respond to bridging therapy compared with those who did respond (any delayed neurotoxicity 12.0% vs 6.0%; parkinsonism 5.0% vs 0.5%). Of note, 95% of parkinsonism cases occurred in bridging therapy nonresponders, despite high post–CAR T-cell response rates, underscoring that inadequate disease control before infusion increases toxicity risk even when efficacy is preserved.

Within this same study, excessive lymphocyte expansion, reflected by peak absolute lymphocyte count (ALC), emerged as another potentially modifiable risk factor. Patients who developed parkinsonism had significantly higher ALCs at Days 7, 14, 21, and 28. A peak ALC >3000/μL was associated with a 12-fold increased risk of parkinsonism.

This immune signature may reflect overactive CAR T-cell proliferation, potentially driven by high tumor burden or a primed immune environment. When combined with the finding that nonresponse to bridging therapy also independently predicted neurotoxicity, a biologic pattern begins to emerge: High disease burden entering CAR T-cell infusion may result in hyperactive CAR T-cell expansion, increasing the risk of off-target, delayed neurologic effects.

Of importance, ALC is an easily measurable parameter, making it a pragmatic candidate biomarker for early identification of patients at risk. Prospective studies are needed, but these findings raise the possibility of real-time monitoring and preemptive strategies, such as early steroid intervention or dose modulation, in high-risk patients.

Tailoring Bridging Therapy: A Pragmatic, Patient-Centered Approach

Krina K. Patel, MD, MSc
In a single-center retrospective analysis of patients with R/R MM treated with ide-cel or cilta-cel, investigators examined how different bridging therapy strategies and response to bridging therapy influenced outcomes after CAR T-cell therapy. Bridging approaches ranged from minimal or no therapy to conventional regimens, bispecific antibody therapy, and high-dose alkylators, with CAR T-cell expansion kinetics and survival outcomes analyzed in relation to bridging response.

This analysis found that the type of bridging therapy used—whether conventional MM regimens, high-dose alkylators, or bispecific antibodies like talquetamab—was less influential than the simple achievement of a response. This aligns with a commonsense principle: The best bridging therapy is the one that works for the patient in front of us.

Given the variability in prior treatment history, refractoriness, and disease biology, a one-size-fits-all bridging therapy approach is not feasible in practice. Instead, bridging strategies must be:

  • Individualized based on prior response patterns and expected tolerability
  • Balanced to achieve rapid disease control while minimizing additive toxicity
  • Focused on delivering patients to CAR T-cell infusion in the best possible condition

This philosophy emphasizes early planning, careful selection of agents that have not previously failed, and consideration of novel short-acting therapies where feasible.

Clinical Implications and Future Opportunities

Noopur Raje, MD

Together, these findings encourage a proactive, risk-adapted approach to delivering CAR T-cell therapy. Rather than reacting to complications as they arise, we can begin to identify patients at risk before they even receive their infusion, using 2 modifiable and measurable parameters:

  • Bridging therapy response status
  • Postinfusion ALC

This opens the door to targeted interventions, more nuanced monitoring, and ultimately, more predictable and safer CAR T-cell delivery.

Your Thoughts
Have you adjusted your clinical approach to bridging therapy based on its emerging role in predicting certain CAR T-cell–associated toxicities? What tools or strategies would help you better anticipate complications in patients being referred for CAR T-cell treatment? Share your perspective to help us collectively refine care.

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Does your institution have a protocol for bridging therapy prior to CAR T-cell therapy in MM?

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