Dr Sands on Toxicities Associated With Tarlatamab in SCLC

"CRS happens acutely [with the use of tarlatamab]. It’s managed acutely and generally resolves fairly acutely as well."

Jacob Sands, MD, associate chief of the Lowe Center for Thoracic Oncology and oncology medical director of the International Patient Center at Dana-Farber Cancer Institute; as well as an assistant professor at Harvard Medical School, discussed adverse effects (AEs) associated with the use of DLL3 inhibition in patients with small cell lung cancer (SCLC).

The only DLL3-directed therapy currently available in clinical practice for SCLC management is tarlatamab-dlle (Imdelltra), which is FDA-approved for patients with extensive-stage disease. Although the safety profile of tarlatamab may appear concerning based on initial review, in clinical practice, the toxicities associated with this agent have proven to be relatively straightforward to manage in most patients, Sands said. The principal toxicity requiring attention is cytokine release syndrome (CRS), he emphasized. CRS occurs in approximately 50% of patients treated with tarlatamab, representing a relatively high incidence, he stated. This phenomenon reflects immune system activation, he explained. However, most cases are grade 1 in severity, manifesting only as fever, which is typically managed effectively with acetaminophen, he added. Data from the randomized phase 3 DeLLphi-304 trial (NCT05740566), which compared tarlatamab vs chemotherapy in the second-line SCLC setting, demonstrated that a low percentage of patients who received tarlatamab experienced CRS of grade 2 or higher.

Grade 2 CRS is characterized by hypotension or hypoxemia, requiring interventions like intravenous fluids, supplemental oxygen, corticosteroids, and, in some cases, tocilizumab (Actemra), Sands continued. At this stage, patients are clinically symptomatic, although most patients respond quickly to these measures, he noted. As a result, although grade 2 CRS requires more intensive management, it often resolves without significant complications and is less severe in practice than it may initially appear in protocol descriptions, he contextualized. Importantly, higher-grade CRS remains uncommon with the use of tarlatamab, according to Sands. When CRS does occur, it typically presents acutely, necessitates immediate supportive management, and resolves within a short timeframe, he concluded.