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ASH 2021: Outcomes for Patients with Chronic Lymphocytic Leukemia Previously Treated with a Covalent BTK Inhibitor and BCL2 Inhibitor in the United States: A Real-World Database Study

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Dr. Anthony Mato and colleagues presented this research at the American Society for Hematology annual meeting held December 2021 (ASH 2021).


Covalent or irreversible Bruton’s tyrosine kinase inhibitors (cBTKi) such as ibrutinib and acalabrutinib along with B-cell lymphoma two inhibitors (BCL2i), such as venetoclax, block the activity of pathways that are critical for the survival and growth of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) cells. Therefore, on their own, they are highly effective treatments. Still, they are not curative (meaning they don’t completely eliminate all the cancer cells), so many patients will eventually require additional treatment. Thus far, little is known about how effective treatments are after patients have already been treated with a cBTKi and/or a BCL2i. This study evaluated treatment outcomes in patients with CLL following treatment with these two drug classes using a real-world dataset from the United States.


  • This study was conducted using de-identified electronic medical record data.
  • Eligible patients were diagnosed with CLL and had completed treatment with at least one cBTKi and a BCL2i during the first to third lines of therapy.
  • One hundred twenty-two patients were included in the analysis, and of these, 53% received additional treatment after cBTKi and BCL2i therapy, while 47% did not need further treatment.
  • The most common subsequent therapy was retreatment with a venetoclax-containing regimen (47%).
  • PI3K inhibitors were used in 6% of patients.
  • The median time from the end of cBTKi/BCL2i therapy to discontinuation of subsequent therapy or death was nine months for patients that received additional treatment vs. 11 months for all patients.
  • Based on these results, it seems that patients who require additional therapy after cBTKi/BCL2i therapy have poorer outcomes.


This study shows that there is still a need for better treatment strategies for patients who relapse or become refractory after treatment with cBTKi and BCL2i. Though not explicitly discussed in this abstract, it is possible that the CLL / SLL in these patients has features or mutations that make it more challenging to treat. To improve outcomes for patients, researchers are increasingly studying a multitude of different combination therapies in the hopes that combining drugs with varying mechanisms of action will increase the chances of producing deep remissions for patients.

Here is the link to the ASH 2021 abstract for more details.

Watch Dr. Koffman’s review of the abstract below:

Take care of yourself first.

Ann Liu, PhD