Phase 1/2 study of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic stem cell transplantation (SCT) remains the standard treatment for advanced chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Relapsed disease is the major cause of treatment failure, especially when SCT is given in the setting of advanced disease. Tyrosine kinase inhibitors can be given after transplantation prophylactically or after the detection of minimal residual disease (MRD) to reduce the relapse risk. Posttransplant nilotinib was started after the achievement of sustained engraftment and the resolution of transplant-related toxicities. Nilotinib was continued until progression or unacceptable toxicity. Twenty-two patients with advanced CML (n = 15) or Ph(+) ALL (n = 7) underwent SCT with human leukocyte antigen-matched siblings (n = 11), unrelated donors (n = 7), or alternative donors (n = 4). Sixteen patients were given prophylactic nilotinib maintenance, which was started at a median of 38 days after transplantation. Six patients stopped the treatment because of toxicities (mostly gastrointestinal and hepatic). After nilotinib maintenance, 11 patients achieved (n = 9) or maintained (n = 2) a complete molecular response (CMR), and only 1 of them later relapsed. Four of the 5 patients not achieving CMR relapsed. At a median follow-up of 46 months, 9 patients were alive, and 13 had died. The 2-year overall and progression-free survival rates were 55% (95% confidence interval [CI], 34%-75%) and 45% (95% CI, 25%-66%), respectively. Among the 16 nilotinib recipients, the rates were 69% (95% CI, 46%-92%) and 56% (95% CI, 32%-81%), respectively. The 2-year nonrelapse mortality and relapse rates for all patients were 32% (95% CI, 17%-58%) and 23% (95% CI, 11%-49%), respectively. Nilotinib is relatively safe and effective prophylactic therapy for the prevention of relapse after SCT. It may control MRD and convert patients to CMR, which is associated with prolonged survival. These observations merit further study in larger scale studies.