Impact of COVID-19 on Teclistamab Efficacy in Relapsed/Refractory Multiple Myeloma

Overview

In the MajesTEC-1 trial of teclistamab for relapsed/refractory multiple myeloma (RRMM), 29.1% of patients contracted COVID-19, with a 10.9% mortality rate from the infection. COVID-19 deaths significantly affected survival outcomes, with improved progression-free and overall survival observed when COVID-19 deaths were censored.

Background

Patients with RRMM have a high risk of infections due to immune dysfunction from prior therapies and disease burden. The COVID-19 pandemic posed additional risks, with MM patients experiencing higher infection severity and mortality compared to non-MM populations. The MajesTEC-1 trial, conducted during the pandemic, evaluated teclistamab, a BCMA × CD3 bispecific antibody, in heavily pretreated RRMM patients, providing unique insights into infection risks and treatment outcomes during this period.

Data Highlights

Key Findings

• Among 165 RRMM patients treated with teclistamab, 29.1% experienced COVID-19 infection, with 21.2% having grade 3/4 infections.
• COVID-19-related mortality was 10.9%, with four deaths considered related to teclistamab treatment.
• COVID-19 vaccination uptake during the study was 60%, and unvaccinated patients had higher infection risk and earlier COVID-19 mortality.
• Teclistamab dosing was interrupted in 29 of 48 COVID-19 cases to manage infection risks.
• Censoring COVID-19 deaths revealed improved median PFS (15.1 vs 11.3 months), OS (28.3 vs 21.9 months), and DOR (26.7 vs 21.6 months), indicating COVID-19 significantly impacted survival outcomes.

Clinical Implications

Clinicians should recognize the heightened risk and mortality of COVID-19 in RRMM patients receiving teclistamab, emphasizing the importance of vaccination and infection prevention strategies. Treatment interruptions may be necessary during COVID-19 infection to manage safety. Despite pandemic challenges, teclistamab demonstrates meaningful efficacy in this vulnerable population when COVID-19-related deaths are accounted for.

Conclusion

The MajesTEC-1 trial highlights the significant impact of COVID-19 on outcomes in RRMM patients treated with teclistamab, underscoring the need for vigilant infection management and vaccination to optimize treatment benefits. When COVID-19 deaths are censored, teclistamab shows durable efficacy and survival benefits in this heavily pretreated population.

References

1. MajesTEC-1 Trial Data and Analysis, 2023 -- Effects of COVID-19 on Teclistamab Efficacy in RRMM