尼洛替尼与伊马替尼一线治疗初发慢性髓性白血病患者的比较研究

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. CONCLUSION: Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and significantly improves FFS than imatinib in newly diagnosed patients with CML-CP.