AUTHOR=Poumeaud François , Jaffrelot Marion , Gomez-Roca Carlos , Korakis Iphigénie , Leonardi Giulia , Joly Marine , Mazières Julien , Guimbaud Rosine , Fares Nadim , Alouani Emily 

TITLE=A double-edged sword: unusual multiple severe infections with pralsetinib: a case report and literature review

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1402902

DOI=10.3389/fmed.2024.1402902

ISSN=2296-858X

ABSTRACT=<p>Selective rearranged during transfection (RET) tyrosine kinase inhibitor, pralsetinib, demonstrated clinical efficacy and was well tolerated in lung and thyroid cancers with <italic>RET</italic> gene mutations or fusions in clinical trials. While the latter focused on the risk of pneumonitis, there is a lack of data regarding other types of infectious risks associated with pralsetinib. Herein, we report the case of a 53-year-old patient with a <italic>CCDC6-RET</italic> fusion neuroendocrine tumor, who achieved a partial response with pralsetinib as the fifth-line therapy. Of particular note, during pralsetinib therapy, the clinical course was complicated by five severe infectious events, namely, two oxygen-requiring pneumonias, two distinct spondylodiscitis, and one pneumocystis. Our study highlights the increased risk of any type of opportunistic infectious event with pralsetinib, but not selpercatinib, which is probably caused by off-target JAK1/2 inhibition.</p>