Treatment failure with first line imatinib for patients with chronic myeloid leukaemia in Kenya vs high-income countries.

Abstract

e19068 Background: Chronic Myeloid Leukemia (CML) occurs in all age groups but predominantly in adults. The disease pathogenesis is typified by the presence of BCR-ABL fusion protein coded for by BCR-ABL gene, a product of reciprocal translocation between the long arms of chromosomes 9 and 22 denoted: t(9;22)(q34;q11). This results in leukaemogenic aberrant tyrosine kinase activity. The clinical course is characterized by three phases namely – chronic stable phase, accelerated phase and acute (blastic phase). Imatinib mesylate, an inhibitor of BCR-ABL was approved for treatment of CML and revolutionized its treatment and outcome. There is however a failure rate on imatinib of about 15 % that is partially addressed by second- and third-line tyrosine kinase inhibitors. Methods: We retrospectively collected data on patients treated at the Glivec International Patient Assistance Program (GIPAP), later Max Access Solutions (MAS) clinics at the Nairobi Hospital. Patient demographics, date of diagnosis, disease phase, and date of commencement of imatinib were documented. Treatment failure/switch, and reason were also documented. Results: A total of 1347 patients were included. Mean age was 44.12 years, males were 748 (55.5%), females 599 ((44.5%). All except two (1345) were initiated on imatinib, 206 (15.3%) were switched to second-line therapy due to various reasons including 31(2.3%) due to adverse events, 148 (11%) treatment failure, 15 (1.1%) due to unspecified reasons and 1 due to drug stock-outs. Second line medications were given to 204 patients: 100 (49%) dasatinib, 50 (24.5%) bosutinib, 38 (18.6%) nilotinib, 16 (7.8%) ponatinib. Deaths or losses to follow-up were 181 (13.4%). Conclusions: Overall about 15% failed on imatinib first-line therapy, similar to the experience from high-income countries. The most preferred second-line TKI was dasatinib, based on availability and toxicity profile.