To perform a systematic review and meta-analysis to evaluate the efficacy of Olverembatinib, a novel BCR::ABL1 tyrosine kinase inhibitor (TKI), in refractory chronic myeloid leukemia (CML).

PubMed, Embase and Cochrane database were searched, until June 2024, for randomized clinical trials (RCTs) that assess the efficacy of Olverembatinib in patients with CML, with or without T315I mutation, who have failed at least two prior TKI therapy. The primary outcomes were Major Molecular Response (MMR), Complete Cytogenetic Response (CCyR) and Major Cytogenetic Response (MCyR). Statistical analysis was performed using R-4.4.1. Heterogeneity was examined with I2 statistics.

238 patients were included from 3 RCTs, with follow-up ranging from 0 to 5 years. The pooled analysis revealed an MMR of 0,4205 (95% CI [0,2789 - 0,5765]; p < 0,01); a CCyR of 0,5501 (95% CI [0,3529 - 0,7328]; p < 0,01) and an MCyR of 0,6548 (95% CI [0,4886 - 0,7902]. Heterogeneity was high across all outcomes, with I2 values of 85% for MMR, 88% for CCyR and 85% for MCyR.

The results demonstrate that Olverembatinib has significant efficacy in achieving high rates of MMR, CCyR and MCyR in refractory CML patients. However, the high heterogeneity observed in all three outcomes suggests notable variability across studies. This variability likely stems from differences in baseline characteristics, including the number of prior TKI treatment lines and median treatment duration among study populations. The small number of studies included also contributes to this variability.

Olverembatinib shows promise as an effective treatment option for refractory CML. However, further research is warranted to elucidate the significant heterogeneity observed across studies, optimize treatment strategies, and provide more robust evidence of its efficacy.