• Am. J. Med. Sci. · Jul 2024

    Effect of CYP2C19 polymorphism on response to bortezomib-based therapy in multiple myeloma patients.

    • Lavisha Goel, Pooja Gupta, Lalit Kumar, Thirumurthy Velpandian, Archana Singh, Kalpana Luthra, and Yogendra Kumar Gupta.
    • Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
    • Am. J. Med. Sci. 2024 Jul 1; 368 (1): 182418-24.

    BackgroundBortezomib, a commonly used anti-myeloma drug, is metabolized by liver microsomal enzymes which may be polymorphic and responsible for lack of response in 30% patients. Hence, the association of CYP2C19 polymorphism with treatment response was explored in this study.MethodsTreatment naive multiple myeloma (MM) patients, eligible for bortezomib-based induction treatment, were recruited as per the inclusion - exclusion criteria. The genotyping of CYP2C19 was done using polymerase chain reaction-restriction fragment length polymorphism for *2, *3 and *17 alleles. The incidence and severity of peripheral neuropathy were noted at follow-up visits and graded as per CTCAE criteria ver 5.0.ResultsTotal 220 patients were recruited from August 2016 till May 2021; with a mean age of 55.6 (9.5) years and 65.9% males. Bortezomib+cyclophosphamide+dexamethasone (41.8%) and bortezomib+lenalidomide+dexamethasone (38.2%) were the most prescribed regimens. The CYP2C19 was polymorphic in 38.6%, 2.3% and 23.7% patients for *2, *3 and *17 allele respectively. There were 195 treatment responders and 25 non-responders, and CYP2C19*2 allele was different between responders and non-responders (p = 0.02). All extensive metabolisers (n = 54) were noted to be treatment responders. Peripheral neuropathy was reported by 23.2% patients. The frequency of peripheral neuropathy was somewhat lower in patients having either *2/*2 or *3/*3 allele pattern for CYP2C19 (p = 0.44).ConclusionsPolymorphism in CYP2C19 enzyme is likely to have an impact on bortezomib treatment response and peripheral neuropathy. The study suggests the role of pharmacogenetics in personalised treatment of MM.Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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