MajesTEC-1: Longer Follow-up Teclistamab + Tocilizumab Prophylaxis for CRS in RR multiple myeloma

Longer-term follow-up of patients (pts) receiving prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) in the phase 1/2 MajesTEC-1 study of teclistamab in relapsed/refractory multiple myeloma (RRMM)

Summary:
This study investigates the use of tocilizumab (toci) as prophylaxis to reduce cytokine release syndrome (CRS) associated with teclistamab, a BCMA×CD3 bispecific antibody, in patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM). The cohort received subcutaneous teclistamab with or without prior intravenous tocilizumab, assessing CRS incidence, management, and overall response rates. Results suggest that prophylactic tocilizumab significantly reduces CRS rates without compromising teclistamab's efficacy, supporting potential outpatient use.

Key Points:
• Prophylactic tocilizumab (toci) administration significantly reduces the incidence of cytokine release syndrome (CRS) associated with teclistamab in patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM).
• CRS occurred in 25% of patients who received tocilizumab prophylaxis, with manageable grades (grade 1 in 2 patients, grade 2 in 4 patients); no grade ≥3 CRS events were reported.
• The median time to CRS onset was 2 days, and the median duration was 2 days, managed primarily with additional tocilizumab or steroids, leading to resolution in all cases.
• Common adverse events (any grade/grade 3-4) included infections (79%/25%), neutropenia (63%/63%), and anemia (58%/25%); neurotoxicity was observed in 5 patients (grade 1-2).
• Overall response rate among evaluated patients was 73%, with 59% achieving very good partial response or better.
• Longer-term follow-up did not reveal new safety concerns or compromise teclistamab's efficacy.
• This approach supports potential outpatient administration of teclistamab with prophylactic tocilizumab, currently under investigation in the OPTec study (NCT05972135).
• These findings underscore the clinical utility of tocilizumab in managing CRS associated with teclistamab therapy in RRMM, highlighting its role in optimizing treatment strategies and patient care.

Authors:
Niels W.C.J. van de Donk, Alfred L. Garfall, Lotfi Benboubker, Katarina Uttervall, Kaz Groen, Laura Rosiñol, Jeffrey V Matous, Deeksha Vishwamitra, Caroline Hodin, Tara Stephenson, Keqin Qi, Athena Zuppa, Katherine Chastain, Maria-Victoria Mateos


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