FDA Relaxes REMS, Monitoring Rules for Liso-Cel and Ide-Cel

The FDA's changes to monitoring and regulation requirements for certain CAR T-cell therapies will apply to hematological malignancies.

The FDA has approved label changes to lisocabtagene maraleucel (liso-cel; Breyanzi) and idecabtagene vicleucel (ide-cel; Abecma) that remove Risk Evaluation and Mitigation Strategy (REMS) programs and reduce specific monitoring requirements for the CAR T-cell therapies in patients with B-cell malignancies.¹

Specifically, the FDA has reduced driving restrictions for patients from 8 weeks to 2 weeks following treatment. Patients are also now required to stay within proximity of the health care facility for only 2 weeks following the infusion of CAR T-cell therapy, lowering the prior threshold from 4 weeks.

REMS programs are designed to help mitigate known or potential risks associated with new treatments. The removal of REMS programs for liso-cel and ide-cel reflect the establishment of management guidelines and increased clinical experience by the field to diagnose and manage the risks of adverse effects (AEs) such as cytokine release syndrome (CRS) and neurotoxicities.

“CAR T-cell therapy is a transformational, potentially life-saving option for patients living with blood cancers, and we are working to challenge current practices, assumptions, and barriers that limit access,” Lynelle B. Hoch, president of the Cell Therapy Organization at Bristol Myers Squibb, stated in a news release. “[The] FDA-approved label updates reinforce Bristol Myers Squibb’s continued efforts to collaborate across the health care ecosystem, with the ultimate goal of reaching more patients and democratizing access to cell therapy.”

Liso-cel is a CD19-directed CAR T-cell therapy that has been FDA-approved for the treatment of select patients with B-cell malignancies.² Currently approved indications are as follows:

• adult patients with large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and grade 3B follicular lymphoma who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or relapsed/refractory disease after 2 or more lines of systemic therapy.
• adult patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor
• adult patients with relapsed/refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy
• adult patients with relapsed/refractory mantle cell lymphoma who have received at least 2 prior lines of systemic therapy, including a BTK inhibitor

Ide-cel is a BCMA-directed CAR T-cell therapy that has been approved for the treatment of adult patients with relapsed/refractory multiple myeloma after 2 or more prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.³

In a poster presentation at the 2025 ASCO Annual Meeting, investigators presented findings from an analysis of clinical trial data and real-world findings for liso-cel in the treatment of B-cell malignancies, which showed that data were consistent between clinical trial and real-world experiences, with most CRS and neurotoxicities occurring within the first 2 weeks post-infusion.⁴

Among patients treated with liso-cel in a clinical trial setting who experienced CRS (n = 381), 98% of these instances occurred on or before day 15 following infusion. The median time to onset was 5 days (range, 1-63), and the median time to resolution was 5 days from onset and 9 days post-infusion. In real-world patients who experienced CRS (n = 430), 97% experienced the AE on day 15 or earlier. The median time to onset was 4 days (range, 1-554), and the median time to resolution was 4 days (range, 1-36).

CRS after day 15 occurred in 7 patients treated in clinical trials and 15 patients treated in the real-world setting. These AEs were grade 1 (n = 5) and grade 2 (n = 2) among patients in clinical trials; they were grade 1 (n = 9), grade 2 (n = 2), grade 3 (n = 1), and unknown (n = 3) among real-world patients.

Neurotoxicities occurred in 31% of all patients treated with liso-cel in a clinical trial (n = 220/702), and 88% of these neurotoxicities occurred within the first 2 weeks post-infusion. In the real-world setting, 27% of patients experienced neurotoxicities (n = 234/877), and 95% occurred by day 15.

No grade 5 CRS or neurotoxicities were reported in patients treated in the clinical trials population. Eleven patients in the real-world population—derived from the Center for International Blood and Marrow Transplant Research registry—experienced grade 5 CRS and/or immune effector cell–associated neurotoxicity syndrome (ICANS) with an onset of on or before day 15 following infusion. Six of these patients had grade 5 CRS, including 3 who had progressive disease reported as the primary cause of death. Four patients had grade 5 ICANS, and 1 patient experienced both CRS and ICANS at grade 5.

References

1. U.S. Food and Drug Administration approves streamlined patient monitoring requirements and removal of REMS programs within Bristol Myers Squibb’s cell therapy labels. News release. Bristol Myers Squibb. June 26, 2025. Accessed June 27, 2025. https://news.bms.com/news/corporate-financial/2025/U-S--Food-and-Drug-Administration-Approves-Streamlined-Patient-Monitoring-Requirements-and-Removal-of-REMS-Programs-within-Bristol-Myers-Squibbs-Cell-Therapy-Labels/default.aspx
2. Breyanzi. Prescribing information. Updated June 2025. Accessed June 27, 2025. https://packageinserts.bms.com/pi/pi_breyanzi.pdf
3. Abecma. Prescribing information. Updated June 2025. Accessed June 27, 2025. https://packageinserts.bms.com/pi/pi_abecma.pdf
4. Kamdar M, Shadman M, Ahmed S, et al. Optimizing post–chimeric antigen receptor (CAR) T cell monitoring: Evidence across lisocabtagene maraleucel (liso-cel) pivotal clinical trials and real-world experience. J Clin Oncol. 2025;43(suppl 16):7026. doi:10.1200/JCO.2025.43.16_suppl.7026