FDA Approves CAR-T Therapy for Marginal Zone Lymphoma, New Myeloma Drug Advances to Phase 2
The FDA has approved Bristol Myers Squibb's CAR-T therapy Breyanzi for relapsed/refractory marginal zone lymphoma, while a novel multiple myeloma drug candidate DTP3 advances to Phase 2 trials after showing promising early results. Both developments represent significant progress in blood cancer treatment, with the marginal zone lymphoma approval based on a 95.5% response rate and the myeloma drug demonstrating selective cancer cell killing without toxicity.
The U.S. Food and Drug Administration has approved Breyanzi (liso-cel), a CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with relapsed or refractory marginal zone lymphoma who have previously received at least two lines of systemic therapy. The approval, announced by Bristol Myers Squibb in December 2025, follows priority review granted in August 2025, with the treatment given as a single infusion and supported by data showing an overall response rate of 95.5% and a complete response rate of 62.1% in the Phase 2 TRANSCEND FL study.
In August 2025, the FDA accepted a supplemental biologics license application for Breyanzi as a potential treatment for adult patients with relapsed or refractory marginal zone lymphoma who have undergone at least two prior systemic therapies, granting it Priority Review under the Prescription Drug User Fee Act with a target decision date of December 5. The application is supported by data from the primary analysis of the MZL cohort in the Phase 2 TRANSCEND FL study, which showed clinically significant benefits for patients treated with Breyanzi.
Meanwhile, a new multiple myeloma drug candidate with a novel mode of action has advanced to Phase 2 patient trials following positive Phase 1 results. The first-in-class investigational drug DTP3, developed to treat multiple myeloma by inhibiting an interaction between two proteins known as GADD45β and MKK7, showed promising results in a Phase 1 trial involving 15 patients, 14 with refractory multiple myeloma and one with diffuse large B-cell lymphoma.
The Phase 1 trial found that DTP3 was well tolerated at doses of up to 45 mg per kg of body weight and yielded preliminary evidence of clinical efficacy. The drug activated apoptosis selectively in the cancer cells in around 50% of patients, with one of two multiple myeloma patients given a dose of 30 mg per kg showing a more than 95% reduction in cancer burden without signs of toxicity. Cancers remained stable in around 50% of patients treated at lower doses.
The trial has now entered Phase 2a, which will test the drug candidate for efficacy at a consistent dose level of 30 mg/kg in a cohort of up to 24 patients with multiple myeloma and 24 patients with diffuse large B-cell lymphoma in hospitals across the UK. The trial is expected to conclude in 2028, with researchers seeking commercial partners to support further clinical development.
Multiple myeloma accounts for about 200,000 annual new cases globally and remains incurable despite recent therapeutic advances. The development of DTP3 builds on research into a pathway called NF-κB, which is hijacked by cancers to promote their own survival, with the drug designed to target a key survival mechanism located downstream of NF-κB.
In the broader landscape of blood cancer drug development, the FDA has issued draft guidance on using minimal residual disease as an endpoint for accelerated approval in multiple myeloma trials. MRD provides a much deeper and more sensitive measure of treatment response than overall response rate or complete response, with the guidance allowing MRD to be used as a primary endpoint in both single-arm and randomized trials.
The global marginal zone lymphoma pipeline constitutes 50+ key companies continuously working towards developing 50+ treatment therapies. Companies developing therapies for marginal zone lymphoma treatment include Carna Biosciences, Hutchmed, Incyte, Innovent, MorphoSys, Beigene, InnoCare Pharma, Beijing Mabworks Biotech Co., MEI Pharma, Inc., Kyowa Kirin, ADC Therapeutics, Loxo Oncology, Adicet Bio, and Celldex Therapeutics Inc. Emerging marginal zone lymphoma therapies in different phases of clinical trials include AS-1763, Amdizalisib (HMPL689), Parsaclisib (IBI376), Tafasitamab, Zanubrutinib, Orelabrutinib, MIL62, Zandelisib, Loncastuximab, LOXO-305, ADI-001, and CDX-1140.