Nilotinib As Second or Third-Line Therapy for Myeloid Chronic Leukemia Chronic-Phase in Mexican Patients

Background.- Nilotinib has 30-fold higher potency and increased selectivity against Bcr-Abl.Fast and deep responses can be achieved with nilotinib after failure to imatinib. In this study, we report the response rates and long-term results of using nilotinib after failure to imatinib or beyond. At the Specialty Hospital CMN "La Raza" nilotinibexperience launching this late 2006, has developed institutional experience.

Objective.- To evaluate the cytogenetic and molecular response to treatment with nilotinib in the second line treatment of patients with CML-CP and its correlation with early molecular-response.

Methods- During the experience with nilotinib as second-line therapy or beyond on CML-CP, 110 CML patients have been treated; established dose of nilotinib for all phase was 400 mg BID. Dose adjustments due toxicity were performed in accordance to previous publications, hematological and no hematological toxicity were scored in conformance to CTCAE v3. Patients were evaluated for hematologic, cytogenetic and molecular responses. Of all patients with CP-CML diagnosed treated with nilotinib, sixty-nine patients were included in the analysis, we selected those who had undergone a molecular evaluation at 3 months. In this study by BCR-ABL mutation status was analyzed. Twenty-seven percent (30 of 110) of the imatinib-resistant patients had BCR-ABL mutation(s) at baseline. One imatinib-resistant patients had the T315I mutation at baseline. The data from 69 patients with CP-CML were analyzed. Distribution of Sokal risk groups were as follows low-16/intermediate-14/high-57/NA-13%.

Results.- Overall, 57 of the 69 patients (83%) of them had a transcript of ≤ 10% at 3 months. Forty-five out of 69 patients (65%) with transcript of ≤10% at 3 months achieved MMR at 12 months, while only 2 of 12 patients (17%) with ratio >10% had MMR, and 83% did not reach the MMR. The EFS by level of transcripts ≤10% at 3 months in 57 patients with 2 events was 96% while in >10% in 12 patients with 4 events was 67%, with an average estimate of time of EFS of 62 vs 43 months respectively. The EFS by MMR at 12 months in 32 patients without events was 100%, while without MMR in 37 patients with 6 events was 84% P=0.022. Nilotinib induced complete cytogenetic responses in 60 percent and 48% molecular responses in the 110 patients treated, 58% of which were major molecular responses, and deep molecular response 42%. To date, 96 of the treated patients remain alive (87%) and continue on treatment.

Conclusions.- Nilotinib (Tasigna) is efficacy and well-tolerated treatment for patients with CML as second-line or beyond in our patients, The 48-month follow-up results show that nilotinib therapy continued to be effective, is comparable to diverse results of other international reports in developed countries.