Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
Brief Report: Intestinal Lymphangiectasia With Selpercatinib and Pralsetinib Treatment.
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Rubio-Perez Jaime, Daher Sameh, Lin Sabrina T, Wilhelm Clare, Ye Ling Feng, Tole Maria Camila, Repetto Matteo, Preeshagul Isabel, Ng Kenneth, Riely Gregory, Kris Mark G, Gibson Jamie, Shia Jinru, Das Jeeban P, Iasonos Alexia, Faleck David, Drilon Alexander
Аннотация
BACKGROUND: Selective RET inhibitors (SRIs) have durable activity in RET fusion-positive lung cancers. Insidious side effects may emerge with long-term use. This is the first systematic analysis of intestinal lymphangiectasia (IL), an underrecognized disorder characterized by dilated intestinal lacteals and potential lymph leakage, in this population.
METHODS: Patients with RET-altered lung cancers treated with selpercatinib or pralsetinib were eligible for this retrospective analysis. IL was classified as possible (radiologic findings), probable (radiologic and clinical findings), and definite (radiologic, clinical, and endoscopic or pathologic findings).
RESULTS: Of 113 patients, 33 (29%) had IL-associated radiologic findings. Cumulative incidence at 1, 3, and 5 years was 11% (95% confidence interval [CI], 6%-18%), 27% (95% CI, 19%-36%), and 31% (95% CI: 22%-41%), respectively. Prior immune checkpoint inhibitor exposure was associated with IL risk (hazard ratio, 3.02; 95% CI: 1.53-5.96; p = 0.001). Among patients with IL-associated findings, IL was classified as possible, probable, and definite in 25%, 60%, and 15%, respectively. Median time from SRI initiation to radiologic findings (involving the ileum and duodenum in 67% and 24% of patients with IL, respectively) was 15 months. Radiologic findings were associated with additional clinical findings (e.g., gastrointestinal symptoms, hypoalbuminemia, hypocalcemia, third spacing) in 76% of patients. All patients with assessable endoscopic biopsies had mild lacteal dilatation. IL improved radiologically and clinically in 64% of patients after SRI dose reduction or discontinuation.
CONCLUSION: Drug-induced IL occurs with selpercatinib or pralsetinib treatment. The frequency increases with longer drug exposure. Serial monitoring is essential and when necessary, dose modification. Most cases do not lead to treatment discontinuation.
METHODS: Patients with RET-altered lung cancers treated with selpercatinib or pralsetinib were eligible for this retrospective analysis. IL was classified as possible (radiologic findings), probable (radiologic and clinical findings), and definite (radiologic, clinical, and endoscopic or pathologic findings).
RESULTS: Of 113 patients, 33 (29%) had IL-associated radiologic findings. Cumulative incidence at 1, 3, and 5 years was 11% (95% confidence interval [CI], 6%-18%), 27% (95% CI, 19%-36%), and 31% (95% CI: 22%-41%), respectively. Prior immune checkpoint inhibitor exposure was associated with IL risk (hazard ratio, 3.02; 95% CI: 1.53-5.96; p = 0.001). Among patients with IL-associated findings, IL was classified as possible, probable, and definite in 25%, 60%, and 15%, respectively. Median time from SRI initiation to radiologic findings (involving the ileum and duodenum in 67% and 24% of patients with IL, respectively) was 15 months. Radiologic findings were associated with additional clinical findings (e.g., gastrointestinal symptoms, hypoalbuminemia, hypocalcemia, third spacing) in 76% of patients. All patients with assessable endoscopic biopsies had mild lacteal dilatation. IL improved radiologically and clinically in 64% of patients after SRI dose reduction or discontinuation.
CONCLUSION: Drug-induced IL occurs with selpercatinib or pralsetinib treatment. The frequency increases with longer drug exposure. Serial monitoring is essential and when necessary, dose modification. Most cases do not lead to treatment discontinuation.