Dosing challenges for chemotherapy and immunotherapy in congenital achondroplasia: a case report and literature review

INTRODUCTION: Currently, no established guidelines exist for dosing chemotherapy or immunotherapy in patients with achondroplasia. CASE: A 69-year old female with congenital achondroplasia was diagnosed with stage IV non-small cell lung carcinoma type adenocarcinoma, with high Tumor Mutational Burden and 20% programmed death-ligand 1 expression. The patient received carboplatin dose based on renal function utilizing measured creatinine clearance, pemetrexed based on body surface area and pembrolizumab at a fixed dose of 100mg for body weight <65 kg. The doses of carboplatin and pemetrexed were adjusted after the first cycle based on therapeutic drug monitoring (TDM). The treatment was generally well tolerated, with the exception of grade 2 neutropenia, which resolved after a one-week delay of the third treatment cycle. A favorable clinical response was achieved after four treatment cycles. CONCLUSION: Given the uncertainty regarding the accuracy of dosing algorithms in patients with congenital achondroplasia, TDM may support dose optimization and attainment of adequate drug exposure.