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- Title
Alkylating Agent-Induced High Tumor Mutational Burden in Medullary Thyroid Cancer and Response to Immune Checkpoint Inhibitors: Two Case Reports.
- Authors
Moog, Sophie; Lamartina, Livia; Bani, Mohamed-Amine; Al Ghuzlan, Abir; Friboulet, Luc; Italiano, Antoine; Lacroix, Ludovic; Postel Vinay, Sophie; Tselikas, Lambros; Deschamps, Frédéric; Bonnet, Baptiste; Pani, Fabiana; Baudin, Eric; Hadoux, Julien
- Abstract
Background: Patients with metastatic medullary thyroid cancer (MTC) who progressed under tyrosine kinase inhibitors can benefit from an alkylating agent such as dacarbazine or temozolomide. Patient Findings: We describe two patients with metastatic MTC who developed a hypermutant phenotype after alkylating agent treatment. This phenotype was characterized by a high tumor mutational burden (TMB) and a mutational signature indicative of alkylating agent mutagenesis (single-base substitution 11). Both patients received immune checkpoint inhibitors, with partial morphological responses, clinical benefit, and progression-free survival of 6 and 9 months, respectively. Summary and Conclusions: Based on the described observations, we suggest that a hypermutant phenotype may be induced after alkylating agent treatment for MTC and the sequential use of immunotherapy should be further explored as a treatment option for MTC patients with increased TMB.
- Subjects
IMMUNE checkpoint inhibitors; MEDULLARY thyroid carcinoma; THYROID cancer; ALKYLATING agents; DACARBAZINE; IMMUNE response; PROTEIN-tyrosine kinase inhibitors; IPILIMUMAB
- Publication
Thyroid, 2023, Vol 33, Issue 11, p1368
- ISSN
1050-7256
- Publication type
Article
- DOI
10.1089/thy.2023.0144