Evaluation Of Response To Imatinib Mesylate Therapy Among Chronic Myeloid Leukaemia Patients As Seen In Nairobi, Kenya

Abstract

Background: Without treatment, chronic myeloid leukemia (CML) progresses from a chronic phase (CP) followed by an accelerated phase (AP) and then to the blast phase (BP).The approval of imatinib mesylate by the Food and Drug Administration (FDA) in 2001 marked a change in paradigm CML therapy. Therapy with tyrosine kinase inhibitors (TKI) reduces the CML residual disease to levels which cannot be of detected by cytogenetic or hematologic testing but only by molecular testing using quantitative polymerase chain reaction(Qrt-PCR). Guidelines by both National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) establish response milestones for TKI treatment. Early attainment of minimal residual disease in the treatment with TKIs is predictive of a favourable prognosis. There are 1200 CML patients currently enrolled in the Gleevec International Patient Assistance Programme (GIPAP) in Kenya. Their molecular response to imatinib therapy is unknown. This study aimed at determining the molecular response to imatinib among CML patients enrolled in the GIPAP programme in Nairobi. Objective: To determine the response to imatinib mesylate among CML patients attending the GIPAP clinic at the Nairobi Hospital; Kenya. Methods: This was a cross-sectional descriptive study carried out at the GIPAP clinic in Nairobi Hospital. Chronic myeloid leukaemia patients who had been on imatinib for not less than 18 months and gave consent were enrolled consecutively into the study until a sample size of 207 was attained. The investigator reviewed the patients and perused through their records to extract socio-demographic, clinical and laboratory data including breakpoint cluster region-Abelson leukemia virus (BCRABL) transcript level at baseline and after 18 months of imatinib therapy. Information was entered in a data entry form, transferred into a data base and analyzed using STATA version 13 SE. Results: Out of 215 participants studied, 210 (97.7%) were in chronic phase. Most of the participants, 138 (64%) had a low EUTOS risk score at entry. The median period of clinic follow up was 4.7 years. Almost a half, 105 (49 %) of the participants had been exposed to hydroxyurea. The median duration to initiation of imatinib was 4.9 weeks. Majority of the participants, 180 (84%) achieved complete hematologic remission (CHR) at 3 months. More than a half of the participants reported having missed a dose. One third 74 (34%) of the participants had optimal response, 34 (20%) had treatment failure and 98 (46%) had suboptimal response. High EUTOS score (24% vs. 42%, p = 0.011), prior treatment with hydroxyurea (35% vs. 56%, p <0.001) and poor adherence (26% vs. 69%, p <0.001) were associated with suboptimal response and treatment failure. Conclusion: This study demonstrated that a minority of the participants, 74 (34%) had an optimal treatment response and 34 (20%) had treatment failure. A high EUTOS score, prior treatment with hydroxyurea and poor adherence were associated with poor response to imatinib therapy. Recommendation: Measures should be instituted to improve access and adherence to treatment with imatinib among CML patients attending the GIPAP clinic.