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Therapeutic options for large B-cell lymphoma relapsing after CD19-directed CAR T-cell therapy

Bone Marrow Transplantation volume 59, pages 162–170 (2024)Cite this article

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Abstract

In recent years, chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment landscape for large B cell lymphoma (LBCL), demonstrating remarkable efficacy and ushering a new era of therapeutic possibilities. However, a subset of patients may not achieve the desired response with CAR T. This review examines strategies aimed at optimizing outcomes for patients who relapse or progress after CAR T. Available data on utilization of CD19-directed monoclonal antibodies and antibody drug conjugates have shown limited efficacy in this setting. Moreover, bispecific antibodies have also emerged as an alternative therapy in relapsed and or refractory LBCL, but long-term follow up treated cases post-CAR T failure are lacking. Several observational studies have shown efficacy of allogeneic hematopoietic cell transplantation, but attainment of a complete remission prior to allografting is a prerequisite to achieve durable remissions. As we navigate the intricate landscape of treatment of post CAR T failure, it becomes evident that this represents a therapeutic challenge which necessitates a multifaceted approach.

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Fig. 1: Treatment algorithm for the treatment of patients with R/R LBCL after CAR T therapy.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Connecticut, Farmington, CT, USA

    Samantha El Warrak

  2. Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA

    Mohamed A. Kharfan-Dabaja & Madiha Iqbal

  3. Blood and Marrow Transplantation Program, Medical College of Wisconsin, Milwaukee, WI, USA

    Mehdi Hamadani

  4. Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA

    Julio Chavez

  5. Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Razan Mohty

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SEW, MAKD, MI, MH, JC, and RM designed, wrote, edited and approved the final version of the manuscript.

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Correspondence to Razan Mohty.

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RM, SEW, and MI have no COI to declare; MAK-D: Research/grant: Novartis, Bristol Myers Squibb and Pharmacyclics. MH: Research Support/Funding: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite. Abbvie, Caribou, Genmab. Speaker’s Bureau: ADC Therapeutics, AstraZeneca, BeiGene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR; JC: Consulting: BMS, Kite/Gilead, Novartis, GenMab, Genentech, AstraZeneca, Janssen, AdiCet, Cellectis, BeiGene, ADC Therapeutics. Honoraria: Lilly, AstraZeneca, BeiGene. Research Support: Merck, Janssen, AstraZeneca, Adaptive

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El Warrak, S., Kharfan-Dabaja, M.A., Iqbal, M. et al. Therapeutic options for large B-cell lymphoma relapsing after CD19-directed CAR T-cell therapy. Bone Marrow Transplant 59, 162–170 (2024). https://doi.org/10.1038/s41409-023-02176-0

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