Prophylactic Tocilizumab May Limit Tarlatamab Toxicities for High-Risk Patients With Extensive-Stage Small Cell and Neuroendocrine Lung Cancer
Key Clinical Takeaways:
- Key Outcomes: In real-world use, tarlatamab was associated with higher-than-trial rates of CRS (53.3%) and ICANS (23.3%) among patients not receiving prophylactic tocilizumab, including grade ≥ 3 events in 10% each; prophylactic tocilizumab markedly reduced CRS and eliminated ICANS.
- Design / Population: This retrospective, single-center analysis included 40 patients with SCLC or high-grade neuroendocrine carcinoma treated with tarlatamab after prior therapy, with toxicity predictors assessed using logistic regression in patients not receiving prophylactic tocilizumab.
- Clinical Relevance: These findings highlight the importance of real-world toxicity monitoring with tarlatamab and support consideration of prophylactic tocilizumab, particularly in patients with elevated LDH, liver metastases, or cardiometabolic comorbidities.
Second-line tarlatamab therapy for patients with extensive-stage small cell lung cancer (ES-SCLC) and neuroendocrine lung cancer was associated with higher CRS and ICANS rates in real-world settings than observed in trials, according to a retrospective real world analysis. Prophylactic tocilizumab may be a potential strategy to mitigate these toxicities among high-risk patients.
Tarlatamab has been utilized as a second-line treatment option for patients with ES-SCLC following progression on platinum-based chemoimmunotherapy. Although clinical trials demonstrated encouraging anti-tumor activity, real-world data characterizing its safety profile remain limited.
In order to assess safety, this retrospective analysis evaluated 40 patients with SCLC or high-grade neuroendocrine carcinoma treated with tarlatamab at Moffitt Cancer Center between May 2024 and February 2025. Patient demographics, clinical characteristics, laboratory parameters, and treatment-related toxicities—including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS)—were assessed. Predictive models for CRS and ICANS were developed using Firth logistic regression in the subset of patients who did not receive prophylactic tocilizumab.
The median patient age was 66.5 years; 55% were male, and the majority (87.5%) had an ECOG performance status of 0 to 1. Among patients who did not receive prophylactic tocilizumab (n = 30), CRS occurred in 53.3% and ICANS in 23.3% following Cycle 1 Day 1, with grade ≥ 3 events observed in 10% for each toxicity. Treatment discontinuation due to severe CRS or ICANS occurred in 3 patients, including 2 treatment-related deaths and 1 transition to hospice care. In contrast, among patients who received prophylactic tocilizumab (n = 10), only 1 developed grade 2 CRS and no ICANS events were reported. Elevated lactate dehydrogenase levels and the presence of liver metastases were independently associated with CRS risk, while LDH also predicted grade ≥ 2 CRS. Comorbid diabetes and cardiovascular disease were independently linked to ICANS.
Overall, “Tarlatamab is associated with higher CRS and ICANS rates in real-world settings than observed in trials, study authors concluded, adding, “Prophylactic tocilizumab may mitigate these toxicities in high-risk patients and should be considered for incorporation into treatment protocols.”
Source:
Joshi U, Ong F, Meltzer D, et al. Optimizing tarlatamab delivery in small cell and neuroendocrine lung cancer: real-world insights into step-up dosing and prophylactic tocilizumab use. Clin Lung Can. Published online December 5, 2025. https://www.clinical-lung-cancer.com/article/S1525-7304(25)00326-2/abstract
