Journal of Leukemia
Open Access

Abstract

Long-Term Outcomes of Tyrosine Kinase Inhibitors Treatment for Chronic Myeloid Leukemia

Alvarado Ibarra M , Mena Zepeda V, Alvarez Vera J, Ortiz Zepeda M, Jimenez Alvarado R and Lopez Hernandez M

Introduction: Chronic myeloid leukemia Ph+ (CML) is a myeloproliferative neoplasm that originates in a pluripotent and abnormal bone marrow cell, consistently associated with the BCR-ABL fusion gene, 1 located on the Ph chromosome, represents 15% of all leukemias. Treatment has evolved along with the disease using alkylators, antimetabolites, immunomodulators, and tyrosine kinase inhibitors (TKI), that have significantly improved patient survival, including ponatinib, effective for the T315I mutation.

Objective: To know the overall survival and progression-free survival of TKIs (imatinib, nilotinib and dasatinib) in patients with Ph+ CML treated at the CMN Hematology Service "20 de Noviembre" ISSSTE, in a long-term followup.

Patients and Methods: Over 15 years with Ph+ CML from 1999 to 2016 not treated with ITQ and without contraindication to receive them. Those who rejected this treatment were not included. Those who died due to some comorbidity not related to CML, those who switched to progenitor hematopoietic stem cell transplantation, those who refused to continue receiving TKIs or when treatment was suspended for administrative reasons (loss of right to institutional insurance).

Results: A total of 82 patients were analyzed. In 37% of the patients, the initial treatment was chemotherapy. Patients who achieved molecular remission had a mean of 5 months before starting TKIs. Imatinib was only used in the first line (n=65), nilotinib was the majority in the second line (n=18) and dasatinib was the only one indicated in the third line (n=8). Molecular remission was profound in 26 patients and greater in 24%. No remission was achieved in four patients. The PFS, recorded from the start of any TKIs, was likely 0.83 to 156 months of follow-up. The OS was 0.92 to 191 months.

Conclusions: Imatinib was used in our hospital in 2001. Until then, it was treated with hydroxyurea, busulfan, or cytarabine + IFN. The patients who started receiving TKIs during the first two months, after diagnosis, had OS as well as those who were delayed more than this time. The depth of remission was related to the time at which TKIs administration was started and only reached remission in those who started it within the first six months. We found no significant difference between the three TKIs. Failure to respond was the most frequent condition. The months elapsed waiting for a response was greater than 6 months, which is prolonged, particularly in the case of the passage from first to second line. This delay, in our cases, is related to the lack of second-generation TKIs. More than half had molecular remission, major or profound, with one or more of the inhibitors employed. However, the SG is not affected by the existence of cytogenetic or molecular remission.