Complications of Modern Immunotherapy (CAR-T and BsAb), a Single Centre Experience

Introduction: immunotherapy represents a revolutionary therapeutic approach in the current era of malignant disease treatment. However, this therapy has its own pitfalls and risks, including immune complications such as Cytokine Release Syndrome (CRS), Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), immunosuppression and subsequent infections.

Aim: The analysis aimed to evaluate the incidence of infectious and immune complications (CRS, ICANS) in patients treated with modern immunotherapy (Chimeric Antigen Receptor T-Cell Therapy (CAR-T) and bispecific antibodies (BsAb) of the antiCD20 and antiBCMA/GPRC5D groups), to compare the findings across agents and to detect IgG antibody levels along with the incidence of infectious complications.

Methods. This was a retrospective analysis of all incomers treated with BsABs and CAR-T. Data were extracted from the hospital information system.

Results. Eighteen patients were treated with CAR-T (here (14/18) 77.8% with a diagnosis of non-Hodgkin's lymphoma (NHL), (4/18) 22.2% with a diagnosis of multiple myeloma (MM)) and 63 patients were treated with BsAb (here (38/63) 60.3% with a diagnosis of NHL, (25/63) 39.7% with a diagnosis of MM). The target antigen was BCMA/GPRC5D in 35.8%, CD20 in 46.9% and CD19 in 17.3%. The overall incidence of CRS was 63%, with a maximum severity of grade 2, in 21% of patients, and with the most significant prevalence in CAR-T, 94.5%. The incidence of ICANS was observed in 38.9% of patients, exclusively with CAR-T therapy for B-NHL. Infectious complications were observed in 74.1% of patients overall, with a median incidence of 79 days after therapy. The most common type of infection, given the epidemiological situation, was COVID-19 (44%), followed by respiratory infections (30%), urinary infections (3%), sepsis (8%), aspergillosis (2%), and unspecified infections (13%). Any grade infection was observed in both BsAb groups (antiBCMA/GPRC5D and antiCD20) with an overall proportion of infectious complications (88% vs. 81.6%) and a similar proportion of each grade (grades 3-5: 32% vs. 31.6%). The median IgG concentration at 3 months post-treatment was 3.65 g/L in the antiBCMA/GPRC5D BsAb group, 3.13 g/L in the CAR-T group and 5.15 g/l in the antiCD20 BsAB gourp. Percentage of patients indicated for substitution across immunotherapy groups; antiBCMA/GPRC5D BsAb (76%), CAR-T (38.9%), antiCD20 BsAb (21.1%).

Conclusion: Infectious complications remain a significant source of morbidity and mortality in patients treated with modern immunotherapy. Patients treated with antiCD20 and antiBCMA/GPRC5D showed different levels of IgG antibodies, but the observed incidence of infectious complications was similar in both types.

Belada:Pharmycyclics: Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Charles University Hospital Hradec Kralove, Czech Republic: Current Employment; Abbvie: Consultancy; Takeda: Consultancy, Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Swixx: Consultancy; GIlead Sciences: Consultancy; Novartis: Consultancy; Eli Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Orphosys: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding. Zak:University Hospital Hradec Kralove: Current Employment. Radocha:Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; GSK: Consultancy; BMS: Consultancy, Honoraria; Jonhson & Jonhnson: Consultancy, Honoraria.