Prophylactic tocilizumab to mitigate cytokine release syndrome in patients receiving tarlatamab: A single-center exploratory experience informed by bispecific antibody safety data.

Abstract

8082 Background: Tarlatamab, a bispecific T-cell engager (BiTE) targeting CD3 on T cells and DLL3 on small cell lung cancer (SCLC) cells, represents a major advance in treating relapsed or refractory SCLC. By activating T cells to release cytotoxic cytokines, it induces tumor cell death but carries risks such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). In the phase 2 DeLLphi-301 trial, CRS occurred in up to 53% of patients treated with Tarlatamab. Current inpatient step-up dosing protocols aim to mitigate toxicity but add cost and complexity, particularly for immunocompromised patients. Tocilizumab, an interleukin-6 (IL-6) receptor inhibitor used for CRS, has demonstrated prophylactic benefit in mitigating cytokine-related adverse events with other BiTEs such as teclistamab. We hypothesized that prophylactic tocilizumab could similarly reduce Tarlatamab-related CRS in SCLC without compromising efficacy. Methods: We retrospectively analyzed 32 consecutive SCLC patients treated with Tarlatamab at our center. Tocilizumab (8 mg/kg) was administered 1 hour prior to the first Tarlatamab dose when approved by insurance. CRS incidence, grade, rescue interventions, treatment discontinuations, and cost implications were evaluated. CRS grading followed standard consensus guidelines. Results: Among 32 treated patients, 29 (90.6%) received prophylactic tocilizumab, and 3 did not. CRS developed in 3 of 29 patients (10.3%) who received pre-treatment—two grade 1 and one grade 2. In contrast, all 3 patients (100%) who did not receive pre-treatment developed CRS—two grade 1 and one grade 2. Overall, CRS occurred in 6 patients (18.8%). All cases resolved after tocilizumab rescue therapy, and no treatment discontinuations occurred. Conclusions: Prophylactic tocilizumab substantially reduced CRS incidence among SCLC patients receiving Tarlatamab, suggesting a feasible and safe mitigation strategy. Compared with historical data from DeLLphi-301 (53% CRS incidence), this cohort exhibited markedly lower toxicity rates with prophylactic IL-6 blockade. To our knowledge, this represents the first clinical evidence supporting IL-6 blockade before Tarlatamab administration. Despite the upfront drug cost ($2,800–$5,100 per dose), prevention of CRS-related hospitalizations offers significant economic benefit (estimated $11,000–$200,000 per event based on grade). Limitations include small sample size, lack of randomization, and single-center design. Nonetheless, these findings underscore the potential of integrating tocilizumab prophylaxis into standard Tarlatamab protocols and warrant larger prospective studies to confirm safety, efficacy, and cost-effectiveness.