Efficacy Of Nilotinib On Imatinib-Resistant OR-Intolerant Chronic Myeloid Leukemia

Objective:Chronic myeloid leukemia (CML) is a kind of malignant hematopoietic stem cell hyperplastic disease. Imatinib, the first generation of tyrosine kinase inhibitors (TKIs), has achieved good efficacy as first-line treatment on CML. However, some patients can’t benefit from Imatinib for resistance or intolerance to Imatinib. Nilotinib, the second generation of TKIs, has been used among the patients who are resistant or intolerant to Imatinib. We aimed to evaluate the efficacy of Nilotinib on Imatinib-resistant or-intolerant CML.Patients and Methods:We retrospectively analyzed12CML patients resistant or intolerant to Imatinib who switched to Nilotinib from January2007to November2013in Qilu Hospital, Shandong University. All the patients got Ph(+) and/or BCR/ABL fusion gene. Of them,10patients were in chronic phase,1patient was in accelerate phase and1patient was in blastic phase. The median duration of Imatinib treatment was21(5-66) months. The main reasons to switch to Nilotinib were Imatinib treatment failure (10cases), and Imatinib intolerance (2cases).2BCR/ABL kinase domain mutations were detected, including Y253H and C475YFSX11mutation. All of12patients were treated with Nilotinib400mg q12h. During the treatment analysis of blood, bone marrow, genetics and molecular examinations were taken regularly to evaluate the efficacy.Results:The median duration of Nilotinib therapy was16(1-32) months up to November2013. Of8Imatinib-resistant patients in chronic phase,5cases achieved complete cytogenetic remission (CCyR).2cases didn’t achieve partial cytogenetic remission (PCyR).1patient have no evaluation of efficacy because of short time of therapy (1month).3patients achieved main molecular remission (MMR) or complete molecular remission (CMR) of5patients with CCyR.2Imatinib-intolerant patients achieved CCyR and CMR repectively after Nilotinib treatment.1case in accelerate phase was primary resistant to Imatinib with Y253H mutation. After12months treatment of Nilotinib, the patient didn’t achieved PCyR and died.1patient in blastic phase was Ph(+) with additional chromosome abnormality. The patient didn’t achieve PCyR after2months of Nilotinib treatment and died. The adverse events included hematologic adverse events, rash, headache and so on.Conclusions:Nilotinib is effective and well tolerant for the CML patients who were resistant or intolerant to Imatinib.