Abstract 495P
Background
Mutations of DPyD can result in severe adverse reactions and even death in patients receiving fluoropyrimidines, a common chemotherapeutic agent. The spectrum of mutations and their clinical significance in Indians is not well characterized to date; resulting in unexpected toxicity in many patients.
Methods
To describe the spectrum of DPyD mutations in the screened population. To find causal associations between mutations and possible Treatment Related Adverse Events (TRAE) METHODOLOGY A Prospective analysis of all patients tested for DPyD deficiency between 1st January 2023 to 30th July2024, for a period of 4 chemo cycles. The incidence of TRAEs were noted and correlated with DPyD screening result.
Results
Of the 169 cases screened, 151 were analysed; of whom toxicity (any grade) was seen in 52(34.3%) patients [Grade III/IV toxicity-19 (12.5%), death-5 (Three in DPD wild type and two in the poor metaboliser mutation group)]. Nineteen required hospitalisation. Pre-emptive testing was done in 135 and for 16 after toxicity. Mutations were detected in 99 cases (65.5%); of which 34(22.5%) patients had TRAEs - any grade; and 12 (7.9%) - grade III/IV - including 2 deaths; both were harbouring poor metaboliser mutation. In the remaining 52 (34.4%) wild-type patients, 18 (11.9%) had toxicity (any grade); and 7 (4.6%) - grade III/IV- including 3 deaths. The most common mutation was c. 85T>C DPYD*9A p.C29R (69 out of 99; 69.6%) followed by c.2194G>A DPYD*6 p.V732I (14 out of 99; 14.4%). Among *9A mutatnts, 23 out 69 (33.33%) had any grade toxicity and 8 out of 69 (11.6%) had grade III/IV toxicity; and among *6 mutants, 7 out of 14 (50%) had any grade toxicity and 2 out of 14 (14.2%) had grade III/IV toxicity; which did not correlate with CPIC recommendations except in 2 cases. Both the patients who had non-functional mutations succumbed.
Conclusions
The spectrum of DPyD mutations in our study seemed different from the Dutch and CPIC databases. The toxicity did not correlate with CPIC recommendations, needing an entirely different dose modification guideline for Indian population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.