Prophylactic Tocilizumab Reduces CRS in Teclistamab-Treated RRMM Patients

Overview

In a single-center study of 53 relapsed/refractory multiple myeloma patients treated with teclistamab, prophylactic administration of tocilizumab prior to the second step-up dose significantly reduced the incidence and severity of cytokine release syndrome (CRS). This approach also decreased immune effector cell neurotoxicity syndrome (ICANS) rates and did not compromise treatment response or increase severe neutropenia.

Background

Teclistamab is a bispecific antibody targeting CD3 and BCMA, approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM). While effective, teclistamab is frequently associated with CRS, occurring in over 70% of patients, mostly low grade but occasionally severe. Current FDA guidelines recommend hospitalization during step-up dosing to monitor for CRS. Tocilizumab, an IL-6 receptor antagonist, is used to treat CRS, but its prophylactic use to prevent CRS during teclistamab therapy has not been well studied.

Data Highlights

Key Findings

• Prophylactic tocilizumab reduced all-grade CRS incidence from 73.3% to 26.3% in patients receiving teclistamab.
• The majority of CRS events in the prophylactic cohort were low grade (grade 1), with only one patient experiencing grade 3 CRS.
• ICANS incidence decreased from 20% to 5.3% with prophylactic tocilizumab, all grade 1 and concurrent with CRS.
• Prophylactic tocilizumab did not increase the incidence of grade 3 or 4 neutropenia compared to historical data.
• Response rates remained robust with a 70% overall response rate and 50% achieving VGPR or better in the prophylactic cohort.
• No hospital readmissions within 14 days occurred in patients receiving prophylactic tocilizumab, supporting outpatient administration feasibility.

Clinical Implications

Prophylactic administration of tocilizumab prior to the second step-up dose of teclistamab can significantly reduce the incidence and severity of CRS and ICANS without compromising efficacy or increasing severe neutropenia. This strategy may enable safer outpatient administration of teclistamab, reduce steroid use, prevent dose delays, and decrease hospital readmissions. Clinicians should consider timing of tocilizumab to optimize CRS prevention, especially given some CRS events occur after the first step-up dose.

Conclusion

Early prophylactic tocilizumab effectively mitigates CRS and ICANS in heavily pretreated RRMM patients receiving teclistamab, maintaining treatment efficacy and safety. These findings support its incorporation into clinical practice to improve patient outcomes and facilitate outpatient therapy.

References

1. MajesTEC-1 Study 2022 -- Teclistamab in RRMM
2. FDA Package Insert -- Tecvayli (Teclistamab)
3. ASTCT Consensus Grading 2019 -- CRS and ICANS
4. Recent Reports 2023 -- Correlation of Early Immune Response and Outcomes