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Bispecific Antibodies for Non-Hodgkin Lymphoma Treatment

  • Lymphoma (JL Muñoz, Section Editor).
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion Statement

While there have been numerous advances in the field of non-Hodgkin lymphoma (NHL) over the last decade, relapsed and/or refractory (R/R) NHL remains a challenge and an area with unmet needs. T-cell redirecting immunotherapeutic approaches including chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs) have the potential to revolutionize NHL therapy. BsAbs target CD3 on T-cells and CD19 or CD20 on malignant B-cells and have shown promises as a novel immunotherapy for NHL. The development of CD19 × CD3 BsAbs such as blinatumomab was met with significant challenges due to dose-limiting neurologic side effects. However, several CD20 × CD3 BsAbs including odronextamab, mosunetuzumab, glofitamab, and epcoritamab emerged recently. They have favorable toxicity profiles, with reduced cytokine release syndrome and neurotoxicity. In addition, all these BsAbs have demonstrated very promising efficacy in R/R NHL. With expansion and registrational studies actively ongoing, approvals of these agents for R/R NHL are anticipated in the near future. Some important questions pertinent to future clinical development of BsAbs include when and how to best utilize BsAbs in the management of R/R NHL, whether there is a role of BsAbs in treatment-naïve NHL, and how to combine BsAbs with other therapies. For example, whether BsAbs can be combined with cytotoxic chemotherapy effectively remains to be seen. A plethora of clinical studies will be needed to help address these questions, some of which are already ongoing. In addition, how do BsAbs compare to CAR T-cell therapy and how to choose and sequence between BsAbs and CAR T-cell therapy need to be addressed. While many of these critical questions remain to be answered in clinical studies, we believe the future of BsAbs in the NHL is very bright.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Allison M. Bock MD, Grzegorz S. Nowakowski MD & Yucai Wang MD, PhD

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  2. Grzegorz S. Nowakowski MD
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Correspondence to Yucai Wang MD, PhD.

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Conflict of Interest

Allison M. Bock declares that she has no conflict of interest. Grzegorz S. Nowakowski has received research funding (paid to his institution) from Celgene/Bristol-Myers Squibb, Roche, Genentech, and NanoString Technologies, and has received compensation for service as a consultant from MorphoSys, Celgene/Bristol-Myers Squibb, Roche, Genentech, Kite Pharma, Ryvu Therapeutics, Selvita, Curis, Karyopharm Therapeutics, Bantam Pharmaceutical, Daiichi Sankyo, Zai Lab, Incyte Corporation, TG Therapeutics, and Blueprint Medicines. Yucai Wang has received research funding (paid to his institution) from Incyte Corporation, InnoCare, LOXO Oncology, Novartis, and Genentech; and has served on advisory boards for Incyte Corporation, LOXO Oncology, Eli Lilly, and TG Therapeutics. All compensation was paid directly to his institution.

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Bock, A.M., Nowakowski, G.S. & Wang, Y. Bispecific Antibodies for Non-Hodgkin Lymphoma Treatment. Curr. Treat. Options in Oncol. 23, 155–170 (2022). https://doi.org/10.1007/s11864-021-00925-1

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