Comparison of Major Molecular Responses Achieved at 12 Months with Imatinib Versus Newer Generation Tyrosine Kinase Inhibitors in Philadelphia Chromosome Positive Chronic Myeloid Leukemia Patients: A Systematic Umbrella Review and a Meta-analysis

Abstract

Background: Chronic myeloid leukemia is myeloproliferative disorder that arise due to overexpression of ABL tyrosine kinase enzyme as a result of fusion of ABL gene on chromosome 9 to BCR on chromosome 22. This leads to neoplastic proliferation of myeloid stem cells. It is treated with BCR-ABL Tyrosine kinase inhibitors. Efficacy is measured using Major molecular response. MMR is reached if the standardized BCR-ABL: ABL gene ratio less than 0.1% in blood or bone marrow.  The faster MMR is reached the faster the recovery.

Objective: To compare major molecular response at 12 months achieved with the use of first versus newer generation Tyrosine Kinase Inhibitors in Philadelphia (9:22 translocation) chromosome positive Chronic myeloid leukemia, utilizing an Umbrella review of existing papers on the topic.

Methodology: An Umbrella review and a meta-analysis were performed on meta-analysis conducted, comparing MMR at 12 months with Imatinib vs new generation TKIs. PubMed and Mendeley search engine were used to search for meta-analysis published on the afore mentioned topic. Their results (Risk ratio of MMR 12) were pooled to produce an overall result. Publication bias and forest plot were drawn. Quality assessment of studies included was performed using AMSTAR2 tool. PRISMA flow diagram was also drawn to simplify the search and screening strategy. Protocols were registered at Open science framework. Research was self-funded.

Results:3 studies met the inclusion exclusion criteria. The proportion of patients achieving MMR with Newer generation Tyrosine kinase inhibitors were greater than those with First generation (Imatinib), RR: 1.58 CI: 1.49, 1.68.

Conclusion: Newer generation TKIs are better in achieving MMR at 12 months than Imatinib.