[Comparison of nilotinib vs imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase].

ABSTRACT

Objective: To compare the cytogenetic and molecular responses, outcomes and severe hematologic toxicity of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: Newly diagnosed CML-CP patients were consecutively recruited from January 2006 to December 2018 who received nilotinib and imatinib as first-line treatment. Clinical data were retrospectively analyzed. Results: A total of 524 patients were classified into 439 (83.8%) receiving imatinib and 85 (16.2%) receiving nilotinib. Comparing with imatinib group, patients in nilotinib group were much younger (P=0.019) and more with intermediate and high Sokal risks (P<0.001) , WBC ≥100×10(9)/L (P<0.001) , HGB<120 g/L (P<0.001) , blast cells in bone marrow (P=0.026) , splenomegaly (P<0.001) by physical examination at diagnosis, and longer interval from diagnosis to TKI treatment (P=0.003) . With a median TKI duration of 57 (range 3-153) months, the probabilities of complete cytogenetic response (CCyR) (P=0.011) , major molecular response (MMR) (P=0.001) and MR(4.5) (P=0.046) were much higher in nilotinib group than those in imatnib according to each risk group. There is no statistical significance on probabilities of failure free survival (FFS) , progression free survival (PFS) and overall survival (OS) at 6 years between the two groups. Multivariate analyses showed that imatinib was an adverse factor associated with achieving CCyR (OR=0.6, 95% CI 0.5-0.8, P=0.001) , MMR (OR=0.6, 95% CI 0.5-0.9, P=0.032) and MR(4.5) (OR=0.6, 95%CI 0.5-0.9, P=0.032) and poor FFS (OR=1.9, 95%CI 1.0-3.4, P=0.041) . In addition, Sokal score was an independent factor affecting cytogenetic and molecular responses, treatment failure, disease progression and survival. Male, WBC ≥100×10(9)/L or HGB<120 g/L at diagnosis were significantly associated with lower cytogenetic and molecular response rates and/or poor FFS. The severe hematologic adverse events were not associated with different TKIs. Conclusions: Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and significantly improves FFS than imatinib in newly diagnosed patients with CML-CP.