OA-51: Preliminary Recommendations for Prevention and Management of Infections, Hypogammaglobulinemia, and Neutropenia During Treatment With Teclistamab Based on Experience From the MajesTEC-1 Study

Introduction: Bispecific antibodies targeting B-cell maturation antigen (BCMA) may contribute to increased infection risk among patients with relapsed/refractory multiple myeloma (RRMM) due to on-target, off-tumor toxicity. Teclistamab is the only approved BCMA×CD3 bispecific antibody with a personalized, weight-based, and flexible dosing schedule for the treatment of triple-class exposed RRMM. Based on experience from the phase 1/2 MajesTEC‑1 study, we provide preliminary recommendations for managing potential infections during teclistamab treatment.

Methods: Patients (N=165) received subcutaneous teclistamab 1.5 mg/kg weekly following a step-up dosing schedule. Patients must have had no evidence of serious bacterial, viral, or fungal infections to initiate treatment with teclistamab. Infection monitoring, prophylaxis, and management, including intravenous immunoglobulin G (IVIG), were per institutional guidelines.

Results: At median follow-up of 21.7 months (range, 0.3–32.7), infections occurred in 129 patients (78.2%) overall (grade 3/4 in 86 patients [52.1%]). Twenty patients (12.1%) died due to infections (17 from COVID-19). Median time to first onset of any grade and grade 3–5 infections was 1.7 and 4.2 months, respectively. Overall, 70.9% of patients had ≥1 immunoglobulin G (IgG) value < 400 mg/dL; 45.5% received IVIG. Grade 3/4 neutropenia occurred in 65.5% of patients at a median of 2.3 months; 53.3% of patients received granulocyte colony-stimulating factor (G-CSF).

Conclusions: Based on MajesTEC-1, IVIG (administered every 3–6 weeks) is indicated for IgG < 400 mg/dL and for serious or recurrent/chronic infections. Patients should be screened for hepatitis B and C and receive all appropriate vaccinations (including COVID-19) before starting teclistamab. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes viruses is recommended; other prophylactic antimicrobials should be administered per institutional guidelines. G-CSF should be considered for grade ≥3 neutropenia with infection/fever and/or grade 4 neutropenia. Due to the increased infection risk with BCMA-targeting bispecific antibodies, patients should be closely monitored for a range of infection types throughout teclistamab treatment.
Data previously presented at the 9th World Congress on Controversies in Multiple Myeloma (COMy) 2023.