Examining Nilotinib to Prevent Post-Transplant Relapse in Patients With Ph+ Leukemia

In previous research published in Blood, Paul A. Carpenter, MBBS, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, and co-authors determined that using the first-generation tyrosine kinase inhibitor (TKI) imatinib early after allogeneic hematopoietic cell transplantation (alloHCT) is feasible for relapse prevention in patients with Philadelphia chromosome–positive (Ph+, BCR/ABL expressing) leukemia. However, because alloHCT may be performed in patients who are resistant or intolerant to imatinib, the authors questioned whether using the second-generation TKI nilotinib could improve outcomes specifically for these patients.

In a Letter to the Editor published in Blood, Dr. Carpenter and colleagues presented updated results from a single-arm study of 57 patients enrolled between September 2008 and September 2013. Patients were eligible for inclusion if they were undergoing alloHCT, had BCR/ABL-expressing acute lymphocytic leukemia (ALL) or chronic myeloid leukemia (CML), and were being treated with myeloablative conditioning. Patients were excluded if they had a cardiac condition or used a pacemaker.

During the study, 17 patients became ineligible to begin relapse prophylaxis, leaving 40 patients in the final intent-to-treat (ITT) population: 11 were imatinib-resistant or -intolerant, and 29 were imatinib-sensitive. Thirty-two patients had ALL (median age = 42 years; range = 11-65 years) and eight had CML (median age = 51 years; range = 18-54 years).

Following alloHCT, patients who were intolerant or refractory to imatinib began nilotinib 300 mg (for adults) or 175 mg/m2 (for children) once- or twice-daily prior to 80 days post-transplant and were increased to a higher dose on day 81. The study also included patients with imatinib-sensitive leukemia who began imatinib 400 mg (for adults) or 260 mg/m2 (for children) once-daily, then, at 81 days post-transplant, switched to nilotinib 400 mg (for adults) or 230 mg/m2 (for children) once- or twice-daily (depending on tolerability) for one year.

After a median follow-up of 4.15 years (range not provided), 67.5 percent of the ITT population were alive at three years, and 15 percent had relapsed. Nine patients died during observation (from relapse [n=4], non-relapse mortality [n=3], and unknown causes [n=2]), for a one-year all-cause mortality rate of 22.5 percent.

Thirty-one patients (78%) experienced 110 adverse events (AEs), and 21 patients experienced serious AEs. The most common AEs were thrombocytopenia (47.5%), lymphocytopenia (27.5%), elevated aspartate and alanine transaminase (25%), anemia (17.5%), neutropenia (17.5%), and cytomegalovirus viremia (17.5%). The researchers noted that 43 AEs (39%) were either possibly, probably, or definitely related to nilotinib.

Thirteen patients completed nilotinib therapy at the target 400 mg dose, and “all are alive without relapse,” the authors reported, adding that four of those patients were imatinib-resistant or -intolerant. Also, 11 of the 24 patients who tolerated nilotinib ≥400 mg could also tolerate the twice-daily dosing. They concluded, though, that “a larger prospective controlled trial would be necessary to confirm this apparent high rate of efficacy, [and] optimizing TKI therapy for high-risk Ph+ leukemia after HCT remains challenging.”

The study is limited by its small patient population and single-arm design.

The study was funded partly by an award from Novartis Pharmaceuticals, which is the manufacturer of nilotinib.

The authors report no other conflicts.


Carpenter PA, Johnston L, Fernandez HF, et al. Post-transplant feasibility study of nilotinib prophylaxis for high-risk Philadelphia chromosome positive leukemia. Blood. 2017 July 11. [Epub ahead of print]