Medically reviewed by Dr. Brian Koffman
The Bottom Line:
Blood samples from patients participating in a phase 2 clinical trial of acalabrutinib and obinutuzumab suggest that acalabrutinib treatment helps to normalize the skewed T cell profiles seen in CLL.
Who Performed the Research and Where Was it Presented:
Dr. Alicia Vaca from MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2022.
Background:
In chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), the immune system goes off the rails. Because of immune system dysfunction, patients with CLL / SLL are more susceptible to infections, have an increased risk of autoimmune conditions, and have an increased risk of developing secondary cancers. Since CLL is a cancer of B cells, it makes sense that B cell function would be compromised, but it is also essential to know that T cells are also dysfunctional in CLL. Specifically, CLL alters the numbers and functional capacity of different types of T cells. CLL cells increase the number of regulatory T (Treg) cells, which can suppress cellular immune responses. Additionally, the T cells of CLL patients exhibit signs of “exhaustion,” which accompany functional deficits such as reductions in their ability to kill germs or cancerous cells. Ibrutinib is known to improve the skewed T cell profile seen in CLL, but it is unclear if acalabrutinib has similar effects.
Methods and Participants:
Serial blood samples were obtained from 12 patients participating in a phase 2 clinical trial of acalabrutinib and obinutuzumab to treat CLL. Samples were taken at baseline, after one week, and after 1, 3, 6, and 12 months of continuous acalabrutinib treatment (with monthly obinutuzumab added during months 3-9). Six age-matched healthy donors were analyzed for comparison. T-cell subsets were characterized by flow cytometry.
Results:
- Untreated patients with CLL had elevated levels of helper T-cells (CD4+) and cytotoxic or killer T-cells (CD8+).
- After 12 months of treatment with acalabrutinib, these T cell levels normalized.
- In CLL, there are increased numbers of two specific T cell subsets, T follicular helper cells (Tfh) and Tregs, associated with unfavorable outcomes.
- Treatment with acalabrutinib for 12 months significantly reduced both Tfh and Treg numbers and reduced cytokine production by these cells.
- Acalabrutinib treatment reduced the proliferation of CLL cells as well as the proliferation of Tregs.
Conclusions:
This study suggests that acalabrutinib treatment helps to normalize the skewed T-cell profiles seen in CLL. These findings are similar to ibrutinib’s effects on T cells. This suggests that it might not be an “off-target” effect of a particular BTK inhibitor. Instead, it might result from decreased T cell interference from the reduced burden of CLL because the therapy works. Does this mean any treatment that knocks back the CLL could improve T cell function? Maybe, but more research is needed before we have a definite answer.
Links and Resources:
Here is the actual ASH abstract: Changes in the T Helper Cell Compartment during Treatment with the BTK Inhibitor Acalabrutinib
Take care of yourself first.
Ann Liu, PhD
