More control over side effects of bispecific antibodies

Several publications have recently appeared providing guidance on the management of toxicity in the treatment of multiple myeloma with bispecific antibodies. Improved prevention of cytokine release syndrome sometimes makes it possible to treat patients without hospitalization, says hematologist Prof. Dr. NWCJ (Niels) van de Donk (UMC Amsterdam).

Immunotherapies targeting cancer cell surface antigens, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies, have significantly advanced treatment outcomes for patients with multiple myeloma (MM). Data from phase I/II trials of teclistamab (MajesTEC-1), elranatamab (MagnetisMM-1), and talquetamab (MonumenTAL-1) show an overall response rate (ORR) of approximately 65% ​​and a median progression-free survival (PFS) of approximately 11 months in extensively treated patients with relapsed/refractory multiple myeloma (RRMM).^1-3

Meanwhile, bispecific antibody therapy is frequently associated with side effects. The MajesTEC-1 study included cytokine release syndrome (in 72.1% of patients; grade 3, 0.6%; none grade 4) and neutropenia (in 70.9%; grade 3 or 4, 64.2%). Infections also occurred relatively frequently (76.4%; grade 3 or 4, 44.8%).

Infection prevention

In light of this, researchers have in recent years focused particularly on studying infections during bispecific antibody therapy and measures to prevent them. Van de Donk cites as an example the analysis of the incidence and timing of infections in the MajesTEC-1 study.⁴ This analysis showed that after 22.8 months of follow-up, infection occurred in 80% of patients (grade 3-4 in 55.2%).
Van de Donk: “The conclusion from this is that before patients are started on bispecific antibodies, they should not have an active infection and should be screened for hepatitis B virus, hepatitis C virus and HIV. An individual assessment of appropriate prophylaxis should also be made. Based on the infection profile of the bispecific antibodies, prevention is pneumococci jiroveci Pneumonia (PJP) and herpes simplex/Shingles Recommended for all patients. Patients treated with bispecific antibodies should be closely and continuously monitored and encouraged to actively report signs of infection to enable prompt intervention. Based on the MajesTEC-1 trial, IgG levels should be monitored every 4 to 6 weeks in patients treated with BCMA-targeted bispecific antibodies, and in IgG.