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A double-edged sword: unusual multiple severe infections with pralsetinib: a case report and literature review
François Poumeaud1, Marion Jaffrelot2, Carlos Gomez-Roca3
1Department of Medical Oncology, Oncopole Claudius Regaud, Toulouse, France.
Abstract:
Selective rearranged during transfection (RET) tyrosine kinase inhibitor, pralsetinib, demonstrated clinical efficacy and was well tolerated in lung and thyroid cancers with RET 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 CCDC6-RET 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.
Insights
Pralsetinib effectively treats cancers with RET alterations but may increase the risk of severe infections. This case report details multiple opportunistic infections during pralsetinib therapy, suggesting a potential link to JAK1/2 inhibition.
Area of Science:
- Oncology
- Pharmacology
- Infectious Diseases
Background:
- Pralsetinib is a selective rearranged during transfection (RET) tyrosine kinase inhibitor approved for cancers with RET alterations.
- Clinical trials have noted pneumonitis as a risk, but data on other infectious risks are limited.
Observation:
- A 53-year-old patient with a CCDC6-RET fusion neuroendocrine tumor received pralsetinib as fifth-line therapy.
- The patient experienced a partial response but developed five severe infections: two pneumonias, two spondylodiscitis, and one pneumocystis.
Findings:
- Pralsetinib therapy was associated with multiple severe opportunistic infections.
- This contrasts with selpercatinib and may be linked to pralsetinib's off-target inhibition of JAK1/2.
Implications:
- Pralsetinib may carry a broader risk of opportunistic infections than previously recognized.
- Monitoring for diverse infections is crucial in patients treated with pralsetinib.
- Off-target JAK1/2 inhibition could be a mechanism driving these infectious complications.
