Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM )retired), MSEd
The Bottom Line:
An ongoing Phase 2 clinical trial is investigating whether preemptive acalabrutinib plus venetoclax can prevent infections in newly diagnosed patients with CLL.
Who Performed the Research and Where Was it Presented:
Dr. Carsten Niemann from the University of Copenhagen and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
When patients are diagnosed with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), they often do not start treatment right away but rather undergo a period of active surveillance (a.k.a. watchful waiting). However, even though they may not yet meet the criteria to begin treatment, some of these patients are at high risk of developing severe infections.
This is because patients with CLL / SLL are immunocompromised, meaning their immune system doesn’t function as well as that of a healthy person. CLL impairs the function of B cells (the immune cells that make antibodies) and T cells (the immune cells that help fight off infections). Other factors, such as age, other health conditions, and medications, can also influence the degree of immune dysfunction. For this study, researchers aimed to investigate whether preemptive treatment with acalabrutinib plus venetoclax could improve immune function in patients newly diagnosed with CLL who are at high risk for infections.
Methods and Participants:
This is an ongoing Phase 2 clinical trial in patients newly diagnosed with CLL. It uses a machine learning-based computer model to identify patients at high risk of severe infections. Patients are randomly assigned to receive either three months of preemptive acalabrutinib-venetoclax or watchful waiting, which is the standard of care. Blood samples are collected at baseline, 12 weeks (end of treatment), and 24 weeks in order to assess various markers of immune function. Infection-free survival and progression-free survival will also be evaluated.
Results:
- Fifteen patients have been randomized thus far.
- Preliminary data from this trial suggests that acalabrutinib-venetoclax may restore some innate immune system function.
- Acalabrutinib-venetoclax reduced levels of inflammatory cytokines compared with watchful waiting.
- Clinical outcomes are expected next year.
Conclusions:
It is still very early on in this trial. Still, the data thus far suggests that early, preventative treatment with acalabrutinib-venetoclax may improve immune function in newly diagnosed CLL patients. We will have to wait and see if these results hold as more patients are enrolled in the trial. We are also interested in learning whether improvements in markers of immune function translate into fewer infections.
Links and Resources:
Watch the interview on the abstract here:
You can read the ASH abstract here: Improved Innate Immune Function upon Preemptive Short-Term Acalabrutinib and Venetoclax in Newly Diagnosed CLL Patients with High Risk of Infections: Translational Findings from the Prevent-Acall Clinical Trial.
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