Dr Rifkin on the Evaluation of Prophylactic Tocilizumab Prior to Teclistamab in R/R Myeloma

Robert M. Rifkin, MD, FACP, medical oncologist/hematologist, Rocky Mountain Cancer Centers, discusses the rationale for, and initial findings from design of, and initial results from a phase 2 single-arm, non-randomized, multicenter, prospective study (NCT05972135) investigating the use of prophylactic tocilizumab (proToci) to reduce the incidence and severity of cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (RRMM) treated with step-up dosing of teclistamab-cqyv (Tecvayli).

The study (NCT05972135) evaluated teclistamab, the only approved BCMA/×CD3–targeted bispecific antibody with weight-based dosing for patients with triple-class exposed RRMMexposed disease. Despite producing, which has shown durable responses in this population, the agent is associated with but significant CRS. This single-arm, non-randomized, multicenter trial focused on the safety endpoint of administering step-up teclistamab dosing in an outpatient setting. The primary endpoint was including the incidence of CRS; key secondary endpoints included the rate of, neurotoxicity, infections, and neutropenia, Rifkin notes, rather than traditional efficacy measures.

Participants aged ≥18 years or older with RRMM relapsed/refractory multiple myeloma and prior exposure to at least four 4 prior therapies were included in the study. , excluding those patients with rapidly progressing disease MM, CNS central nervous system involvement, active infections, or tocilizumab contraindications were not permitted to enroll. Tocilizumab 8 mg/kg IV was administered intravenously (IV) at a dose of 8 mg/kg 2 to 4 hours before the first step-up dose of teclistamab.

The step-up dosing teclistamab SUD regimen involved sequential subcutaneous doses of 0.06 mg/kg, 0.3 mg/kg, and 1.5 mg/kg, followed by a weekly 1.5 mg/kg dose of teclistamab for up to 12 cycles, or until disease progression, or until unacceptable toxicity. Intravenous immunoglobulin was given for IgG levels <400 mg/dL per institutional guidelines.

Initial findings from the first ten 11 patients included in the safety cohort, showed no grade 3 or higher≥3 CRS or immune effector cell-associated neurotoxicity syndrome was reported, NT/ICANS, leading the Data Review Committee (DRC) to recommend proceeding with enrollment supporting continued enrollment. Additionally, no patients required hospitalization due to either tocilizumab or teclistamab. Common adverse events effects (AEs) included fatigue, headache, and neutropenia. One patient experienced a serious unrelated AE and did not complete the regimen.

Rifkin emphasized the trial's unique design, focusing primarily on safety signals and reducing CRS and neurologic events. No CRS or neurotoxicity was observed among the first ten patients, with promising safety results prompting further DRC review.

As this study continues to evolve, ongoing data analysis will aim to determine if proToci prophylactic tocilizumab can improve address AEs associated with teclistamab’s safety profile, making it more. This would make teclistamab more conducive for outpatient administration, and thereby more accessible for patients at community treatment centers.