Efficacy of Nilotinib (AMN107) in Patients (Pts) with Newly Diagnosed, Previously Untreated Philadelphia Chromosome (Ph)-Positive Chronic Myelogenous Leukemia in Early Chronic Phase (CML-CP).

Background: Nilotinib is a novel, oral tyrosine kinase inhibitor with increased selectivity against Bcr-Abl that is approximately 30-fold more potent than imatinib. High response rates have been reported with nilotinib therapy in CML after imatinib failure.

Methods: We evaluated the efficacy of nilotinib as first line therapy in pts with newly diagnosed Ph-positive CML-CP. The primary objective was to estimate the proportion of pts attaining major molecular response (BCR-ABL/ABL ratio ≤0.05% in our lab) at 12 months (mo).

Results: Thirty-two pts have been treated with nilotinib 400 mg orally twice daily for a median of 5 months (mo) (range, 1 to 31 mo). The median age was 47 years (yrs) (range, 24–73 yrs). The Sokal risk at pretreatment was low in 21 (70%) pts, intermediate in 6 (20%), and high in 3 (10%). The rate of complete cytogenetic response [CCyR] (Ph 0%) at 3, 6 and 12 mo compares favorably to those observed in historical controls treated with imatinib 400 mg or 800 mg daily:

The median QPCR with nilotinib at 3, 6, and 12 months were, respectively, 0.52% (range, 0.0–29.5%), 0.03% (range, 0.0–9.13%), and 0.09% (range, 0.0–16.21%). At 3 mo follow-up, major molecular response (MMR; BCR-ABL/ABL ratio ≤0.05%) was observed in 3/22 patients (14%), 7/13 (54%) at 6 mo, and 5/11 (45%) at 12 mo. 12-mo rates of MMR for the historical imatinib groups treated at 400 mg and 800 mg were 24% and 47%, respectively (p=0.02). None of the molecular responses has been lost while on therapy. Grade 3–4 neutropenia was observed in 2 (7%) pts, and thrombocytopenia in 1 (3%). Other grade 3–4 adverse events included elevation of lipase (n=3, 9%), or bilirubin (n=2; 6%), and amylase elevation, back pain, and infection (1 each). Twelve pts had transient treatment interruptions (median 11 days), most frequently due to pain (n=3; musculoskeletal 2, abdominal 1), lipase elevation (n=2). Seven patients had their dose reduced to 400 mg daily, 2 to 200 mg twice daily, and 1 to 200 mg daily due to extramedullary toxicity. Three patients decided to change therapy after 4, 6 and 8 months; 2 switched to imatinib and 1 received SCT.

Conclusion: Nilotinib 400 mg orally twice daily suggest significant efficacy manifested by complete cytogenetic responses in nearly all patients as early as 3 months after the start of therapy with a favorable toxicity profile.