FDA Grants RMAT Status to Allogeneic CAR-T Therapies Cema-Cel and Lasme-Cel
The FDA granted RMAT designation to Allogene’s cema-cel for first-line LBCL consolidation and Cellectis’ lasme-cel for r/r B-ALL. Both allogeneic CAR-T therapies showed promising early efficacy and safety, with cema-cel also receiving Fast Track status.
The U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to two allogeneic chimeric antigen receptor T-cell (CAR-T) therapies: Allogene Therapeutics' cema-cel and Cellectis' lasme-cel. The designations recognize the potential of these off-the-shelf cell therapies to address unmet medical needs in blood cancers.
Cema-cel received RMAT and Fast Track designations as a first-line consolidation therapy for large B-cell lymphoma (LBCL). The FDA based its decision on an interim futility analysis from the ongoing ALPHA3 trial, which showed that 58.3% (7/12) of patients in the cema-cel arm achieved minimal residual disease (MRD) negativity at day 45, compared to 16.7% (2/12) in the observation arm—an absolute difference of 41.6%. Median plasma circulating tumor DNA decreased by 97.7% in the cema-cel group, while the observation group saw a 26.6% median increase. The therapy was well tolerated, with no treatment-related serious adverse events, no cases of cytokine release syndrome, neurotoxicity, graft-versus-host disease, or high-grade infections, and no hospitalizations for treatment-related toxicities; most patients were managed in an outpatient setting. The ALPHA3 trial uses an MRD assay to identify patients at high risk of relapse after first-line chemoimmunotherapy and randomly assigns them to receive a single dose of cema-cel or observation.
Lasme-cel, a CD22-targeting allogeneic CAR-T therapy, received RMAT designation for relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). The decision is supported by Phase 1 BALLI-01 trial data demonstrating promising efficacy and a manageable safety profile. Final Phase 1 results will be presented at the 2026 European Hematology Association Congress on June 13. A pivotal Phase 2 trial is now open for enrollment. Cellectis' CEO stated that the designation recognizes the need for off-the-shelf CAR-T options for patients who cannot wait and strengthens FDA dialogue as the therapy progresses through its pivotal program.
RMAT designation aims to expedite the development and review of regenerative medicine therapies that treat serious or life-threatening conditions and show preliminary clinical evidence of addressing unmet medical needs. The additional Fast Track status for cema-cel further enables enhanced FDA interactions and potential eligibility for rolling review and priority review.