[T-cell recruiting immunotherapies in B-cell lymphoma - the future backbone for all therapy lines?]

The introduction of immunologically targeted therapies has represented a significant advancement in the treatment of B-cell lymphomas, particularly aggressive B-cell lymphoma. CD19 CAR-T cells such as Axicabtagen-Ciloleucel (Axi-cel) and Lisocabtagen Maraleucel (Liso-cel) have been approved since 2022 and 2023, respectively, for second-line therapy of Diffuse Large B-Cell Lymphomas (DLBCL), when there is primary refractory disease or relapse within 12 months after the end of first-line therapy. These therapies result in a significant improvement in progression-free survival compared to the previous standard therapy (salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation). Especially in elderly patients or patients with underlying medical conditions, CAR-T cell therapies like Axi-cel and Liso-cel demonstrate acceptable tolerability and high efficacy.Furthermore, bispecific T-cell-engaging antibodies ("bispecifics") such as Glofitamab, Epcoritamab, and Mosunetuzumab also represent promising treatment options for patients with relapsed disease after failure of second- or later line therapy and show efficacy even in a subset of patients relapsing after CD19 CAR-T cells. However, randomized study results for these substances are not yet available. They are expected to be used in earlier lines of therapy in the future, especially in combination with standard chemotherapy regimens. Common side effects of bispecific antibody therapies are cytokine release syndrome (CRS) and immune-mediated cytopenias, whereas immune-cell associated neurotoxicity syndrome (ICANS) is relatively rare compared to CD19 CAR T cells. In summary, bispecifics represent a novel, highly effective immunotherapy for the treatment of lymphomas with a very favourable toxicity profile.
Competing Interests: Veit Bücklein: has received research funding from Gilead/Kite and Miltenyi Biotec, has received educational grants from BMS, Novartis, Takeda and Roche, and has served as a consultant/advisor to Amgen, Gilead, Novartis, Pfizer, and Priothera. He serves on the speakers’ bureau at Novartis and Pfizer. Marion Subklewe: receives industry research support from Amgen, Bristol-Myers Squibb/Celgene, Gilead, Janssen, Miltenyi Biotec, Morphosys, Novartis, Roche, Seattle Genetics, and Takeda, and serves as a consultant/advisor to AvenCell, CDR-Life, Ichnos Sciences, Incyte Biosciences, Janssen, Molecular Partners, and Takeda. She serves on the speakers’ bureau at Amgen, AstraZeneca, BMS/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, and Takeda. Bastian von Tresckow: Beratertätigkeiten für Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag GmbH, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Roche, Sobi und Takeda; Honorare von AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Lilly, Merck Sharp & Dohme, Novartis, Roche Pharma AG und Takeda; Forschungsförderung der Institution von Esteve, Merck Sharp & Dohme, Novartis, and Takeda; Reise- und Kongressunterstützung von AbbVie, AstraZeneca, Gilead Kite, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, und Novartis
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