Role of Cidofovir in the Treatment of BK Virus Haemorrhagic Cystitis in Patients Undergoing T- Cell Deplete Stem Cell Transplant and Cellular Therapies

Introduction

BK polyoma virus (BKV) is an established cause of haemorrhagic cystitis (HC) in patients undergoing haematopoietic stem cell transplants (HSCT) and cellular therapies (CT). Symptomatic HC is often treated with antivirals and other supportive measures. Reduction in immunosuppressive therapy (IST) is known to ameliorate symptoms. Role of reduction in IST and treatment with cidofovir have not been reported as specific measures in the treatment of symptomatic BKV haemorrhagic cystitis. We present our single centre experience of BKV related HC outcomes and impact of therapy choices.

Methods

A retrospective, descriptive, cross-sectional analysis was conducted using electronic patient records system and other previously stored data. The study included patients above age of 18 years undergoing HSCT or CT, who developed symptomatic BKV infection between Sept 2019 and June 2023. Patient with grade 2+ haematuria or significant viraemia were offered cidofovir monotherapy, where feasible. Symptomatic BKV infection was defined as any degree of HC or dysuria symptoms with or without evidence of end organ damage.

Results

A total of 918 patients received HSCT/CT between Sept 2019 and June 2023. 51 patients had evidence of BK virus infection, which was monitored over a median of 38 days (range 0-634 days). The rate of infection was 5.5%. 30 (59%) were male. The median age at transplant was 54 years (range 25-76). 13 patients (25.5%) were deceased at the time of data collection. 2 patients did not have complete follow up data available. 8 patients had non-malignant conditions and 49 had malignant conditions as indications for HSCT or CT (including CAR-T). 45 patients underwent HSCT of which 41 were allografts, majority were reduced intensity and 40/41 received in-vivo T-cell depletion (TCD: ATG-26 or Alemtuzumab-14). 50% (17) had proven GVHD at the time of detection of BKV. 51 patients had a BK viruria post HSCT, 10 of whom had a BK viruria only without viraemia, while 41 patients had BK viraemia. The median time from HSCT to BK viruria was 35 days (4-189) and to viraemia 45 (6-394). 36/42 patient were receiving IST at the time of BKV detection. Types of TCD didn't have an impact on incidence of HC.

38/51 (74%) patients were symptomatic with haematuria with or without dysuria. 9(17%) had grade 1 haematuria; 22(43%) had grade 2 haematuria ;2(4%) grade 3 and 5(10%) patient had grade 4 haematuria. 1 patient went on to have biopsy-proven BKV nephropathy requiring maintenance haemodialysis. 5/25(20%) patients had abnormal bladder imaging, where data was available. 5 patients needed additional bladder irrigation. 20/51 (39%) patients received cidofovir with Grade2+ HC, and 9 patients with grade2+ HC were treated with supportive care only. 16 patients had a BK viraemia (the range of BK viraemias was log 2.9 to log 5.4) when cidofovir was initiated, 7 of whom had a positive but unquantifiable BK viraemia. 2 patients had increase in BK viraemia, while 14 patients had either <1.0Log decrease or static BK viraemia on Cidofovir (4 patient did not have retesting data available).

10/22 (45%) of the patients had a complete resolution of Grade2+HC symptoms with cidofovir, although the difference was not statistically significant (p-0.95) when compared to patients treated with supportive care alone. Reduction or discontinuation of IST seem to aid symptom resolution, although no direct correlation could be made due to limited available data.

Conclusions:

BKV haemorrhagic cystitis can lead to significant symptom burden in patients undergoing CT or HSCT. Responses to cidofovir were modest in this cohort and drug was well tolerated. Cidofovir seems to reduce HC related symptom burden, although early diagnosis and supportive care remains the mainstay of the current therapeutic approaches.

Kulasekararaj:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharma: Consultancy, Honoraria, Speakers Bureau; Silence Therapeutics: Honoraria; Apellis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Honoraria, Speakers Bureau; Agios: Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Achillion: Consultancy, Honoraria, Speakers Bureau; Akari: Consultancy, Honoraria, Speakers Bureau; Samsung: Consultancy, Honoraria, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; BioCryst: Consultancy, Honoraria, Speakers Bureau. Mehra:Gilead UK: Honoraria, Research Funding; Cidara: Honoraria; Pfizer: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees.