Repurposing Nilotinib for Cytomegalovirus Infection Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Arm, Phase II Trial

Abstract

Platelet-derived growth factor receptor-alpha (PDGFRa) is a critical receptor for cytomegalovirus (CMV) entry into cells, leading to subsequent infection. This trial tested whether PDGFRa inhibition by nilotinib could prevent CMV infection in patients after allogeneic stem cell transplantation (allo-HSCT). Nilotinib (200 mg/day) was given continuously after engraftment, and plasma CMV DNA levels were monitored weekly. The primary endpoint was successful prophylaxis of CMV infection, defined as plasma CMV DNA copies less than 10,000 copies/mL, no anti-CMV treatment initiated, and no clinical CMV disease by day 100. All 37 enrolled recipients and their donors were CMV seropositive. Thirty patients received matched sibling transplants, 15 received nonmyeloablative conditioning regimens, and 15 received antithymocyte globulin as a part of graft-versus-host disease prophylaxis. The median interval from transplantation to nilotinib treatment was 23 days, and the median duration of administration was 76 days. None of the 31 assessable patients had nilotinib-associated grade 3/4 adverse events or nilotinib discontinuation. Twenty-five of 31 assessable patients (80.6%) fulfilled the predefined criteria for successful CMV prophylaxis, and none of them had clinical CMV disease. Only 1 of 6 failed patients developed CMV colitis. Nilotinib is well tolerated in allo-HSCT recipients, and its preliminary efficacy results suggest that blocking CMV entry to prevent CMV infection may warrant further exploration. (ClinicalTrials.gov identifier: NCT01252017.).

Effect of sorafenib maintenance on Epstein-Barr virus and cytomegalovirus infections in patients with FLT3-ITD AML undergoing allogeneic hematopoietic stem cell transplantation: a secondary analysis of a randomized clinical trial

“…PDGFR-ɑ has been reported as a critical receptor required for CMV infection [30]. Interestingly, a recent phase 2 study showed that nilotinib could prevent CMV infection after allo-HSCT by inhibiting PDGFRɑ [31]. However, this study was a single-arm study with a small sample size.…”

A Native Human Monoclonal Antibody Targeting HCMV gB (AD-2 Site I)

“…An unusual new approach to HCMV therapy is based on the observation that the gH/gL/gO trimer uses the PDGF (platelet-derived growth factor) receptor for cell entry [46]. In a single arm Phase 2 trial, a receptor kinase inhibitor (nilotinib, an approved drug for treatment of chronic myeloid leukemia), suppressed HCMV infection in 80.6% of HSCT patients ( N = 37) [47].…”