International Journal of Molecular Sciences (Jan 2024)

Treatment of Double-Refractory Chronic Lymphocytic Leukemia—An Unmet Clinical Need

  • Przemysław Zygmunciak,
  • Tadeusz Robak,
  • Bartosz Puła

DOI
https://doi.org/10.3390/ijms25031589
Journal volume & issue
Vol. 25, no. 3
p. 1589

Abstract

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Recent years have seen significant improvement in chronic lymphocytic leukemia (CLL) management. Targeting B-cell lymphoma (BCL-2) and Bruton’s kinase (BTK) have become the main strategies to restrain CLL activity. These agents are generally well tolerated, but the discontinuation of these therapies happens due to resistance, adverse effects, and Richter’s transformation. A growing population of patients who have previously used both BTK inhibitors and BCL2 suffer from the constriction of the following regimens. This review explores the resistance mechanisms for both ibrutinib and venetoclax. Moreover, we present innovative approaches evaluated for treating double-refractory CLL.

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