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

BACKGROUND: Bortezomib, 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. METHODS: Treatment 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. RESULTS: Total 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). CONCLUSIONS: Polymorphism 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.

Tamsulosin Versus Mirabegron in Relieving Ureteric Stent-Related Symptoms: A Prospective, Double-Blinded, Randomized Controlled Trial.

Introduction Alpha-adrenergic blockers like tamsulosin are widely used in the treatment of stent-related symptoms due to ureteric stents. Recently, mirabegron has emerged as a potential alternative. So, our study aimed to compare the effect of mirabegron and tamsulosin on ureteric stent-related morbidity. Methods In this randomized controlled study, 80 patients undergoing uncomplicated ureteroscopic lithotripsy with double J stenting for ureteric stones were enrolled. They were divided into two groups: Group A (n=40) received mirabegron (25mg) and Group B (n=40) received tamsulosin (0.4mg). Outcomes were assessed using the Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptoms Score (IPSS), and the visual analog pain scale. The t-test and the Chi-square test were utilized to study the efficacy of the interventions across both groups. Results The USSQ urinary symptom score (25.5 vs 33.45; p < 0.001) and body pain score (16.15 vs 26.02; P < 0.001) were significantly lower in the mirabegron group. However, the general health score (17.0 vs 17.28; p = 0.62) and work performance score (7.6 vs 8.0; p = 0.28) did not show a significant difference. The storage symptom score was significantly lower in the mirabegron group (3.98 vs 5.1; p = 0.001). Furthermore, the mirabegron group reported a better quality of life score (2.18 vs 3; p < 0.001). Conclusion Mirabegron has been shown to reduce urinary symptoms associated with ureteric stents and also results in a better quality of life when compared with tamsulosin. However, large-scale, prospective, multicentric studies are further required to holistically evaluate and comprehend the beneficial effects of mirabegron on stent-related morbidity.