In a single-institution phase II trial reported in the Journal of Clinical Oncology, Olson et al found that high rates of response were achieved with third-party BK virus–specific cytotoxic T-lymphocyte therapy (BKV-CTL) in patients with BK virus–associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation (AHSCT) for hematologic malignancies.
As stated by the investigators, “BK virus–associated hemorrhagic cystitis is a common complication of AHSCT, particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BK virus–associated hemorrhagic cystitis typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option.”
Study Details
The trial included 59 consecutive patients with BK virus–associated hemorrhagic cystitis after AHSCT at Memorial Sloan Kettering Cancer Center. They received a single intravenous infusion of most closely HLA-matched third-party BKV-CTLs between October 2015 and September 2019. BKV-CTLs were generated from 26 healthy donors and banked for off-the-shelf use.
Responses to treatment were considered complete responses when there was complete resolution of symptoms and gross hematuria or a decrease from grade 2, 3, or 4 to grade 0 or 1, and partial responses if there were a decrease in hemorrhagic cystitis grade by one grade or more or a one log decrease in viral load on polymerase chain reaction assessment. The most common disease among the 59 patients was acute myeloid leukemia (n = 28, 47.5%), followed by acute lymphoblastic leukemia (n = 10, 16.9%).
Key Findings
KEY POINTS
- By day 14 after first infusion, complete or partial hemorrhagic cystitis response was observed in 40 of 59 patients (67.7%).
- Among evaluable patients, response rates increased to 75.4% and to 81.6% by day 28 and day 45, respectively.
- Responses were durable, with no patients losing previously achieved response.
The initial cell dose was 1 × 105 CTLs/kg (n = 21), which was increased to 2 × 105 CTLs/kg (n = 38) once safety was shown with the lower dose. HLA matches were 1/6 for 8 patients, 2/6 for 26, 3/6 for 16, 4/6 for 8, and 5/6 for 1.
By day 14 after first infusion, complete or partial hemorrhagic cystitis response was observed in 40 (67.7%, 95% confidence interval [CI] = 54.4%–79.4%) of 59 patients. Among evaluable patients, response rates increased to 75.4% (43 of 57 patients; 95% CI = 62.2%–85.9%) and to 81.6% (40 of 49 patients; 95% CI = 68.0%–91.2%) by day 28 and day 45, respectively. The estimated probability of achieving complete response increased over time to 70% (95% CI = 54.5%–81.7%) by day 45. Responses were durable, with no patients losing previously achieved response.
Among 10 patients (5 with no response and 5 with partial response) who received a second infusion with the same or different BKV-CTL line (median of 19 days after first infusion), response occurred in 3 (1 complete and 2 partial responses). Response was achieved in two (1 complete, 1 partial) of five patients receiving a third dose (median of 46 days after first), in each of four (all partial) after a fourth dose (median of 73 days after first), and in one patient (complete) receiving a fifth dose (111 days after first).
No cases of de novo grade 3 or 4 graft-vs-host disease, graft failure, or infusion-related toxicities were observed. BKV-CTLs were identified in blood samples up to 3 months after infusion, with in vivo expansion being predictive of clinical response.
A matched-pair analysis adjusting for prognostic covariate effects using controls who received standard of care showed that BKV-CTL treatment was associated with higher probability of response at all follow-up timepoints. BKV-CTL treatment was also associated with a significant reduction in need for packed red cell transfusions (median = 6 vs 20 units, P = .03).
The investigators concluded: “Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BK virus–associated hemorrhagic cystitis after AHSCT.”
Katayoun Rezvani, MD, PhD, of the Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by philanthropic contributions to The University of Texas MD Anderson Cancer Center AML Moon Shot Program and grants from the National Institutes of Health. For full disclosures of the study authors, visit ascopubs.org.
