Successful Tarlatamab Rechallenge After Recurrent High-Grade Cytokine Release Syndrome in Chromothripsis-Mediated...

Chromothripsis-mediated SCLC (cSCLC) is a distinct subtype of SCLC characterized by wild-type TP53 and RB1, arising in light- or never-smokers. Although data are limited, cSCLC may be associated with poor response to first-line platinum-based chemotherapy. We report the case of a 60-year-old woman with extensive-stage cSCLC who had rapid disease progression after platinum-based chemoimmunotherapy. Second-line therapy with tarlatamab was initiated, which was complicated by high-grade cytokine release syndrome (CRS) after both the initial and second step-up doses. Repeat imaging after these doses demonstrated a substantive early response to tarlatamab. A patient-involved decision was made to continue treatment, and CRS did not recur. This case illustrates the promise of delta-like ligand 3-directed therapy in cSCLC. High baseline disease burden may predispose subjects to more severe CRS without necessitating treatment discontinuation. Early reimaging in these situations may reveal marked treatment response and inform clinical decision-making.