Alkylating Agent-Induced High Tumor Mutational Burden in Medullary Thyroid Cancer and Response to Immune Checkpoint Inhibitors: Two Case Reports.

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.

• Authors: Sophie Moog, Livia Lamartina, Mohamed-Amine Bani, Abir Al Ghuzlan, Luc Friboulet, Antoine Italiano, Ludovic Lacroix, Sophie Postel Vinay, Lambros Tselikas, Frédéric Deschamps, Baptiste Bonnet, Fabiana Pani, Eric Baudin, Julien Hadoux
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 33 Issue 11 Pg. 1368-1373 (11 2023) ISSN: 1557-9077 [Electronic] United States
• PMID: 37698883 (Publication Type: Case Reports, Journal Article)

Chemical References

• Alkylating Agents
• Immune Checkpoint Inhibitors

Topics

• Humans
• Alkylating Agents (adverse effects)
• Carcinoma, Neuroendocrine (drug therapy, genetics)
• Immune Checkpoint Inhibitors (therapeutic use)
• Thyroid Neoplasms (drug therapy, genetics)