Mit Rituximab hat die Immuntherapie bereits vor Jahrzehnten Einzug in die Routinebehandlung
von B-Zell-Lymphomen gehalten. Die Zulassung neuer bispezifischer T-Zell-rekrutierender
Antikörper und der adoptiven Immuntherapie mit CAR-T-Zellen bringt tiefgreifende Änderungen
der Therapiealgorithmen bei aggressiven und indolenten Lymphomen mit sich. Im Folgenden
werden die wichtigsten aktuell zugelassenen T-Zell-rekrutierenden Behandlungsstrategien
vorgestellt.
Abstract
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.
Schlüsselwörter
Immuntherapie - B-Zell-Lymphom - CAR-T-Zellen - bispezifische Antikörper - ADC
Keywords
immunotherapy - B-cell lymphoma - CAR T cells - bispecific antibodies - ADC
