Cell therapy effective, safe for BK virus-associated hemorrhagic cystitis after HSCT
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BK virus-specific cytotoxic T lymphocytes from healthy donors appeared safe and effective for patients with BK virus-associated hemorrhagic cystitis after undergoing allogeneic hematopoietic stem cell transplantation.
Nearly 70% of patients achieved a complete or partial improvement in symptoms 2 weeks after infusion, and more than 80% demonstrated improvement after 28 days, according to an interim analysis of a phase 2 study published in Journal of Clinical Oncology.
“BK virus-associated hemorrhagic cystitis is a common and painful complication of allogeneic HSCT and typically results in painful hematuria, urinary obstruction and renal dysfunction,” Katy Rezvani MD, PhD, Sally Cooper Murray endowed chair in cancer research and medical director of the good manufacturing practice laboratory in the department of stem cell transplantation and cell therapy at The University of Texas MD Anderson Cancer Center, told Healio. “There is no definitive therapeutic option for this complication; therefore, the purpose of this ongoing study is to test the efficacy and safety of immunotherapy with off-the-shelf, most closely HLA-matched third-party, BK virus-specific cytotoxic T lymphocytes [CTLs] to treat BK virus hemorrhagic cystitis in allogeneic HSCT recipients.”
Rezvani and colleagues obtained HLA-matched, third-party, BK virus-specific CTLs from 26 healthy donors and infused them into 59 patients (median age, 47 years; 59.3% men; 55.9% white) who developed BK virus hemorrhagic cystitis after transplant. Patients could receive additional infusions every 2 weeks as needed.
Results showed a rapid response to infusion, with an overall response rate of 67.7% (95% CI, 54.4-79.4) by day 14 of therapy, which increased to 75.4% (95% CI, 62.2-85.9) by day 28 and to 81.6% (95% CI, 68-91.2) by day 45.
Researchers additionally identified BK-specific CD4+ and CD8+ T cells in blood samples up to 3 months after infusion, and in vivo expansion of these cells predicted clinical response.
At a median interval of 19 days, 10 patients with no response (n = 5) or a partial response (n = 5) after the first infusion received a second infusion of the same (n = 6) or a different (n = 4) BK virus CTL line. Among them, one patient achieved a complete response and two achieved a partial response.
At a median 46 days, five patients went on to receive a third infusion, which led to one complete response and one partial response. Four patients received a fourth infusion at a median interval of 73 days and all achieved a partial response. At 111 days after the initial infusion, one patient received a fifth infusion and achieved a complete response.
Researchers observed no cases of de novo grade 3 or grade 4 graft-versus-host disease, graft failure or infusion-related toxicities.
Five patients died due to progression of underlying hematologic malignancy. One-year OS probability was 55.4% (95% CI, 43.9-69.8).
“BK virus hemorrhagic cystitis is a common and difficult-to-treat complication of allogeneic HSCT,” Rezvani said. “BK virus-associated CTLs induced responses in most patients and the responses were rapid and durable. We will now continue enrollment on this study.”
For more information:
Katayoun Rezvani, MD, PhD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: krezvani@mdanderson.org.
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