NeuroVoices: Rosanna Ricafort, MD, on Early Promise of CAR T-Cell Therapy CD19-XT in Multiple Sclerosis

Rosanna Ricafort, MD

Multiple sclerosis (MS) is a chronic autoimmune disease in which the immune system attacks the central nervous system, leading to inflammation, demyelination, and neurodegeneration. Several of the traditional treatment options include immunomodulators and immunosuppressants, such as injectable therapies, oral therapies, and monoclonal antibodies. The idea of cell therapy is an innovative and emerging approach in the MS treatment landscape, focusing on repairing damage and rebalancing the immune system.

At the 2025 Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27-March 1, in West Palm Beach, Florida, investigators presented promising phase 1 study data assessing BMS-986353 (BMS), otherwise known as CD19-XT in patients with relapsing and progressive MS. CD19-XT is an investigational CAR T-cell therapy expressing the CD19-directed CAR used in the FDA-approved lisocabtagene maraleucel (Breyanzi), a medication for types of B-cell lymphoma. Known as Breakfree-2, the trial featured a small cohort of patients who were treated with 5 x 10⁶ CAR T-cells of CD19-XT.

As part of a new iteration of NeuroVoices, Rosanna Ricafort, MD, vice president and senior global program lead for Hematology and Cell Therapy at BMS, sat down to discuss the promising early data from the phase 1 trial. Ricafort highlighted the preliminary findings, including the therapy’s favorable safety profile–no ICANS or dose-limiting toxicities–and evidence of robust B-cell depletion, even at the lowest dose level. Above all, she emphasized the potential of this one-time infusion therapy to transform the MS treatment paradigm, particularly for patients with limited options.

NeurologyLive: How does this therapy function? Discuss some of the advantages it might bring.

Rosanna Ricafort, MD: So, a little bit of background on CD19-XT and, maybe before that, cell therapy in general. When we talk about cell therapy, what we really mean is programming a patient's immune cells to hunt and kill disease-causing cells in the body. CD19-directed CAR T cells are engineered against an antigen expressed on B cells, CD19. This has shown transformational efficacy in the treatment of B-cell malignancies, mainly lymphoma and multiple myeloma, and in recent years, has demonstrated dramatic responses in patients with certain autoimmune diseases.

The underlying rationale for employing CD19 CAR T-cell therapy in autoimmune diseases is to eliminate the autoreactive B-cell compartment causing tissue damage and allow normal B cells to return. This approach achieves deeper B-cell depletion in the periphery and tissue than what monoclonal antibodies can achieve.

Now, a bit about CD19-XT: it's our asset and has the same CD19 construct as our commercially available Breyanzi (lisocabtagene maraleucel), which is approved across a broad array of B-cell malignancies. The XT manufacturing process was designed leveraging our extensive CAR T manufacturing experience, with the aim of shortening manufacturing time, improving production to serve more patients, and enhancing the phenotypic attributes of the CAR T-cell drug product.

How was the study conducted?

The Breakfree-2 study is our phase 1 dose-escalation trial evaluating the safety and tolerability of CD19 XT in patients with multiple sclerosis. The study includes two cohorts: one in relapsing-remitting MS (RRMS) with EDSS scores of 3 to 5.5, and the other in primary progressive MS (PPMS) with EDSS scores of 3 to 6.

What were the major findings from the trial?

It’s still early days, but we’ve reported some initial results at ASH (American Society of Hematology) and are happy to share additional data here at ACTRIMS. So far, we’ve treated four patients—three with relapsing-remitting MS and one with primary progressive MS—all at dose level 1 (5 million cells).

We are encouraged by the preliminary safety and tolerability findings. Notably, there has been no ICANS (immune effector cell-associated neurotoxicity syndrome), which was very important for us to see. There have also been no dose-limiting toxicities, and we’ve only observed transient, low-grade (grade 1) CRS in two patients, which was manageable.

What’s really compelling is that even at the lowest dose level, the pharmacokinetics and pharmacodynamics are promising. We’re seeing robust CD19-XT-cell expansion in evaluable patients, consistent with what we’ve achieved with the approved dose of lysis cell in non-Hodgkin’s lymphoma patients.

In all patients, we’ve seen evidence of deep B-cell depletion, with B cells becoming undetectable in the periphery approximately eight days after a single CAR T infusion. Preliminary efficacy data is encouraging as well—no new enhancing lesions were observed on MRI in the evaluable patients, and one patient even showed improvement in EDSS scores. So, it’s early but exciting data to move forward with.

From a safety aspect, what considerations are you taking to ensure this therapy is effective and not harming patients?

For patients living with MS, particularly those with progressive forms, there are few treatment options available, and none truly treat the underlying disease. Our goal, while early, is to use this therapy to potentially reset the immune system through a one-time infusion, possibly leading to durable, treatment-free disease control.

Safety is absolutely key. At ACTRIMS, we had a lot of discussions with investigators and physicians to identify the greatest opportunities for applying CAR T-cell therapy within the MS treatment paradigm, particularly for relapsing and progressive MS.

We’re also focused on building partnerships between neurologists and hematologists, optimizing communication, and fostering knowledge transfer. This ensures that we’re moving forward in the best possible way, with safety top of mind. Additionally, we’re addressing institutional challenges for CAR T-cell adoption.

We’ve also established the Action Forum, a multi-stakeholder platform where researchers, scientists, clinicians, patient advocates, and care providers can come together to strategize and advance these goals, focusing on scientific excellence, exchange, and ecosystem building.

What are the next steps in advancing this therapy?

We’ll see where the data leads as we continue enrolling patients in this phase 1 study while exploring the potential for a phase 2 trial. We’ve also established an Autoimmunity Cell Therapy Network to advance research in this area. Over the last decade, cell therapy has revolutionized the treatment of blood cancers, offering patients with lymphoma and multiple myeloma durable outcomes—some for nearly 10 years.

While it’s still early, we are excited to bring that same transformational potential to autoimmune and neuroinflammatory conditions, where current treatment options mainly focus on symptom management and inflammation suppression. We’re optimistic about the next steps and look forward to seeing the field progress.

Transcript edited for clarity. Click here for more 2025 ACTRIMS Forum coverage.

REFERENCE
1. Repovic P, Pul R, von Treschkow B, et al. P103. A Phase 1, Multicenter, Single-Arm, Dose-Escalation Study of BMS-986353 (CC-97540), a CD19-Directed Chimeric Antigen Receptor T Cell Therapy Manufactured Using a Next-Generation Process, Evaluating Safety and Tolerability in Patients With Relapsing or Progressive Forms of Multiple Sclerosis (Breakfree-2). Presented at: 2025 ACTRIMS Forum; February 27-March 1; West Palm Beach, FL. ABSTRACT P103.