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Immunotherapies Old and New: Hematopoietic Stem Cell Transplant, Chimeric Antigen Receptor T Cells, and Bispecific Antibodies for the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

  • B Cell NHL, T Cell NHL, and Hodgkin Lymphoma (J Amengual, Section Editor)
  • Published:
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Abstract

Purpose of Review

Diffuse large B cell lymphoma (DLBCL) is curable in a majority of patients; however, a significant portion of patients develop relapsed or refractory disease. High-dose chemotherapy followed by autologous stem cell transplant is the standard approach in appropriately selected patients. Many patients are not candidates for transplant and many who do receive autologous transplant relapse. Therapies which harness T cells including chimeric antigen receptor T cells (CAR-T) and bispecific antibodies are active in this chemotherapy-resistant population. We review the role of autologous and allogeneic stem cell transplant, CAR-T therapy, and bispecific antibodies in the treatment of relapsed or refractory DLBCL.

Recent Findings

Phase I studies of bispecific antibodies directed against CD20 × CD3 have shown activity in heavily pre-treated DLBCL including in patients who have progressed following autologous transplant and/or CAR-T therapy. Two CAR-T products have received regulatory approval in relapsed or refractory DLBCL, with other products in clinical trials. CAR-T treatment has resulted in durable remissions and trials are ongoing to determine if CAR-T should replace autologous transplant as second-line therapy for DLBCL.

Summary

The development of multiple T cell–directed therapies for DLBCL offers new treatment options for chemotherapy-resistant disease. We discuss our approach to relapsed or refractory DLBCL patients and the open question of optimal sequencing of autologous transplant (a current standard treatment), CAR-T therapy (FDA approved), and bispecific antibodies (in clinical trials).

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Acknowledgements

We would like to thank Dr. Roger Strair and Dr. Dennis Cooper for providing expertise and advice in the preparation of this manuscript.

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  1. Division of Blood Disorders, Section of Hematologic Malignancies, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08903, USA

    Anupama Doraiswamy, Mansi R. Shah & Rajat Bannerji

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Correspondence to Rajat Bannerji.

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Anupama Doraiswamy and Mansi R. Shah declare no potential conflicts of interest.

Rajat Bannerji reports research funding from AbbVie, Regeneron, F. Hoffmann-La Roche/Genentech, and Pharmacyclics. His spouse is employed by Sanofi-Pasteur.

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Doraiswamy, A., Shah, M.R. & Bannerji, R. Immunotherapies Old and New: Hematopoietic Stem Cell Transplant, Chimeric Antigen Receptor T Cells, and Bispecific Antibodies for the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma. Curr Hematol Malig Rep 16, 72–81 (2021). https://doi.org/10.1007/s11899-021-00610-y

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