Use of nilotinib to induce responses with 24-month (mo) minimum follow-up in patients (pts) with chronic myeloid leukemia in blast crisis (CML-BC) resistant to or intolerant of imatinib.

Abstract

6510 Background: Nilotinib is a highly potent and selective BCR-ABL inhibitor with efficacy in pts with imatinib-resistant and -intolerant CML in chronic phase (CP) and accelerated phase (AP). Results from pts with CML-BC treated with nilotinib in the phase II 2101 trial are presented. Methods: Pts were treated with nilotinib 400 mg bid. Primary endpoint was confirmed hematologic response (HR). Results: 136 pts with imatinib-resistant (82%) or -intolerant (18%) CML-BC were treated with nilotinib and followed for a minimum of 24 mo. 105 pts had myeloid blast crisis (MBC) and 31 pts had lymphoid blast crisis (LBC). Baseline BCR-ABL mutations were detected in 30% of pts with MBC and 61% with LBC; T315I mutations were detected in 1% of pts with MBC and 7% with LBC. Clonal evolution was detected in 54% of all pts. Best prior response to imatinib was stable or progressive disease in 46%, with only 10% achieving prior complete HR (CHR) and 13% major cytogenetic response (MCyR). Nilotinib resulted in HR in 24% of pts with MBC and 19% with LBC. CHR occurred in 13% of pts with MBC and LBC. Responses were rapid and durable. For pts with MBC, median time to HR was 1 mo, and median duration of HR was 26 mo (range, 1.25-29.08); 60% of pts maintained HR at 24 mo. Median duration of HR was 3.6 mo for pts with LBC and no pt maintained HR at 24 mo. Nilotinib induced MCyR and CCyR in 38% and 30% of pts with MBC and 52% and 32% with LBC, respectively. In MBC pts, median time to MCyR was 1.8 mo, and median duration of MCyR was 11 mo (range, 0.03-29.08); 44% of pts maintained MCyR at 24 mo. Median duration of MCyR was 3.2 mo for pts with LBC and no pt maintained MCyR at 24 mo. Survival was 42% at 12 mo and 27% at 24 mo; 12 pts with MBC and 2 pts with LBC had transplants following nilotinib therapy. Nonhematologic adverse events were generally mild and manageable and similar to those observed in pts with CML-CP. Conclusions: Nilotinib is effective therapy in pts with imatinib-resistant or -intolerant CML-BC, generating rapid and durable responses for pts with MBC. Nilotinib exhibits a favorable safety profile in CML-BC patients. No new safety concerns were observed with 24 mo minimum follow-up. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Novartis Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Genzyme, Novartis