Elucidating Common Toxicities Observed with Immunotherapies in SCLC

Although many adverse effects (AEs) are “few and far between” among patient receiving treatment with immunotherapy for small cell lung cancer (SCLC), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can occur at a higher frequency and severity.

Anne Chiang, MD, PhD, an associate professor of Medical Oncology and Thoracic Oncology, as well as the Associate Cancer Center Director of Clinical Initiatives at Yale School of Medicine, discussed common toxicities associated with immunotherapy treatment for SCLC in an interview with CancerNetwork®. The discussion was contextualized by a presentation at the Chemotherapy Foundation Symposium (CFS), hosted by Physician’s Education Resource®, LLC, where she was presented “Cases and Conversations: Transforming Small Cell Lung Cancer Treatment Through Emerging Evidence and Expert Insights (Spotlight CE Session).”1

She began by highlighting the effective management of toxicities that have emerged with immunotherapy treatment for SCLC, citing success with managing AEs in non–small cell lung cancer (NSCLC) which has been translated to success for SCLC. She explained that for AEs, steroids can be used to mitigate them and then monitoring can be implemented after a treatment-free interval.

Chiang further highlighted unique toxicities that have emerged with tarlatamab-dlle (Imdelltra), which include flu-like symptoms, as well as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Explaining that most patients experience lower grade CRS, she pointed to a low percentage of patients who may experience grade 3 CRS who may require medications to regulate their blood pressure and immune system in an ICU setting. Additionally, she spoke results from the phase 3 DeLLphi-304 trial (NCT05740566),2 which showed that AEs with tarlatamab were generally manageable, with high grade ICANS requiring steroid treatments and a collaboration with neurology.

Transcript:

We have gotten [quite] good at managing these [toxicities] with NSCLC. Typically, we use steroids to mitigate them, and often patients, even after they have been treated with steroids, and they have a treatment-free interval, you can just monitor them, and they may continue to respond. If you consider some of these new therapeutics, such as tarlatamab, which are bispecific antibodies, they have some interesting [adverse] effects that we are learning how to manage… it is like you are getting a flu shot. You get fever, chills, aches and pains. Your blood pressure can be a bit low. You [may] not feel so well. These can be managed with acetaminophen [Tylenol], IV [intravenous] fluids, some oxygen, and steroids.

There are grade 1 or 2 cytokine release syndrome (CRS) [events]. That is most of them; over 50% of patients get grade 1 or 2. There is a small percentage of patients who get grade 3 CRS, and they should be monitored in an ICU setting because they might need some additional medications to support their blood pressure or [may need] tocilizumab [Actemra] to help calm down the immune system, but these are manageable, and we are learning how to do that. Now, the indication is to watch the patients for 24 hours after the infusion for the first 2 weeks. After that, the rest of the doses can be given in the outpatient office. We are working on, at Yale, ways to pilot doing outpatient administration and observation so that patients do not need to be admitted to the hospital.

The field is going to learn how to do this, certainly with the DeLLphi-304 second-line trial of tarlatamab vs investigator choice chemotherapy. That was a positive trial, and it again showed that these [adverse] effects exist but are manageable. Rarely, you can have ICANS, and that, again, is a few percent of patients, and that can manifest as confusion or disorientation, sometimes tremor shakes or some weakness in your arms or legs. Again, we treat that with steroids, and we ask our neuro-oncology colleagues to help follow these patients.

References

1. Rudin CM, Chiang A, Sands JM. Cases and conversations: transforming small cell lung cancer treatment through emerging evidence and expert insights (Spotlight CE Session). Presented at: 43rd Annual Chemotherapy Foundation Symposium (CFS); November 12-14, 2025; New York, NY.
2. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393(4):349-361. doi:10.1056/NEJMoa2502099