Nilotinib in chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib (IM) resistance or intolerance: Longer follow-up results of a phase II study

Abstract

7029 Background: Nilotinib is a potent and highly selective BCR-ABL inhibitor approved for the treatment of Ph+ CML patients (pts) in CP or accelerated phase who are resistant or intolerant to prior therapy including IM. This study evaluated the efficacy and safety of nilotinib (400 mg bid) in CML-CP pts resistant or intolerant to IM. Methods: Primary endpoint was major cytogenetic response (MCyR). Secondary endpoints included complete cytogenetic response (CCyR), complete hematological response (CHR), MCyR duration, overall survival (OS), and safety. Results: CML-CP pts (n = 321, 70% IM-resistant, 30% IM-intolerant with resistance) with a minimum follow-up of 19 months (mos) were evaluated; 72% were treated with ≥600 mg/day IM prior to enrollment. Median duration of prior IM treatment was 32 (<1–94) mos. Median dose intensity of nilotinib (790 mg/day; range 151–1,110 mg/day) closely approximated the planned dose. Nilotinib led to rapid and durable CHR and MCyR. CHR was observed in 94% of pts. 59% achieved an MCyR (2.8 mos median time to MCyR; 56% in IM-resistant, and 65% in IM-intolerant pts), including 73% of pts with a baseline CHR and 44% achieved a CCyR (41% in IM-resistant; 51% in IM-intolerant pts). Responses were durable, with 78% pts maintaining MCyR at 24 mos. Estimated OS rate was 88% at 24 mos. Safety profile did not change with longer follow-up. Most frequent grade (gr) 3/4 biochemical laboratory abnormalities were elevated lipase (17%), hypophosphataemia (16%), hyperglycemia (12%), and total bilirubin (8%) which were transient and clinically asymptomatic. Gr 3/4 non-hematologic AEs were infrequent: rash, headache, and diarrhea occurred in 2% of pts. Most common gr 3/4 hematological laboratory abnormalities were neutropenia (31%), thrombocytopenia (31%), and anemia (10%). Brief dose interruptions were successful in management of most AEs. Pleural or pericardial effusions (gr 3/4) were uncommon (< 1%). Conclusions: These results demonstrate that nilotinib was highly effective, with rapid and durable responses in CML-CP pts failing prior therapy due to resistance or intolerance. Nilotinib was well tolerated with favorable risk/benefit. [Table: see text]