OBJECTIVES: To identify existing literature evidence reflecting the disease burden of CML tyrosine kinase inhibitor (TKI) treatment failure in mainland China.

METHODS: This systematic literature review searched English (MEDLINE, EMBASE, Web of Sciences, Cochrane Library) and Chinese databases (WANFANG, CNKI, VIP) for relevant evidence published in peer-reviewed journals from January 2016 to December 2020. Single-arm meta-analysis and weighted-average methods were used for evidence synthesis. Costs were adjusted to 2020 Chinese yuan (¥).

RESULTS: Pooled annual risks of BCR-ABL1 gene mutations, drug resistance, and treatment intolerance associated with imatinib in the front-line treatment setting were 16.5%, 12.0%, and 6.4%, respectively. Drug resistance (60.9%) and treatment intolerance (24.1%) were the main reasons for TKI treatment failure. Patients with CML treatment failure were characterized by young age (median: 40.4 years), higher male proportion (61.7%), low household income (< ¥2,000/month: 81.6%), and prevalent arthritis (29.9%) and cardiovascular diseases (15.4%). BCR-ABL1 gene mutations in patients with TKI treatment failure included Y253F/H (10.7%), F359V/I/C (8.3%), E255K/V (8.1%), T315I (7.2%), G250E (4.1%), and F317L/V/I/C (2.8%). The pooled annual risk of progression from chronic phase (CP) to accelerated phase (AP)/blast phase (BP) of CML in patients with TKI treatment failure was 23.2%. The pooled rate of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with CML treatment failure was 12.2%. Annual per-capita medical costs associated with CP and AP/BP CML were ¥38,794 and ¥116,618, respectively. Estimated medical costs associated with allo-HSCT and annual medical costs associated with post-HSCT were ¥320,201 and ¥55,799, respectively. The estimated annual per-capita indirect cost for productivity loss associated with CML was ¥26,088.

CONCLUSIONS: Existing literature evidence indicates substantial disease burden of CML treatment failure in China, mainly due to high risk of treatment failure associated with imatinib, young patient age, rapid disease progression after treatment failure, and high medical costs associated AP/BP and HSCT.