Real World Experience using Cidofovir in BK Polyomavirus Haemorrhagic Cystitis following Stem Cell TransplantationAre Generics Equally Efficacious?

Abstract

Introduction: BK Polyomavirus induced Haemorrhagic Cystitis (BKPyV-HC), a well-recognised complication following Haematopoietic Cell Transplantation (HCT), is associated with increased organ dysfunction and mortality. The treatment is a multipronged strategy which includes manipulating immunosuppression and antiviral therapy along with newer advances of virus specific cellular therapy. Cidofovir is a nucleotide analogue of Cytosine that is effective against many Deoxyribonucleic Acid (DNA) viruses and its use has been limited in the past because of cost and toxicity. Aim: To capture real world data on the use of cidofovir in BKPyVHC, post HCT especially with regard to dosage, efficacy, toxicity and predictors of response to therapy. The study compared the efficacy and safety of the innovator molecule of cidofovir with Generic versions. Materials and Methods: This study was a retrospective cohort of 67 patients, who were diagnosed with BKPyV-HC post haematopoietic stem cell transplant, and were treated with cidofovir. The study was conducted at a tertiary care centre at Vellore, Tamil Nadu, India, between 2015 and 2021. BKPyV Polymerase Chain Reaction (PCR) was checked in urine routinely in alternate donor transplants, and if there were typical lower urinary tract symptoms or haematuria in any other transplant setting. Treatment with cidofovir (initially innovator an subsequently generic) was as per physician’s discretion. Results: 985 patients underwent Allogeneic HCT during the study period, of which 67 had BKPyV-HC and were treated with cidofovir (47 with Innovator molecule, 20 with Generic molecule). There was clinical resolution in 47 (70.1%) and mortality in 32 (47.8%) of the cohort. On univariate analysis, risk factors associated with mortality were an absence of clinical resolution (p<0.001), treatment initiation at a higher grade of HC (p=0.032), CD34 cell dose >9x106 /Kg (p=0.029), partial remission of malignancy at the time of transplant (p=0.001), ≤3 doses of cidofovir used (p=0.036), BK log value >log 7 at the time of stopping cidofovir (p=0.021) and toxicity with cidofovir (p=0.036). However, only the absence of clinical resolution was significantly associated (p<0.001) with mortality risk on multivariate analysis. There was no significant difference between the two comparator molecules of cidofovir. Conclusion: Cidofovir is an effective and safe therapeutic option to treat BKPyV-HC with no significant differences seen between the innovator and Generic molecule of Cidofovir in this small series of patients.