Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Atezolizumab-venetoclax–obinutuzumab produced high remission rates, but immune-related side effects limit its usefulness as a frontline CLL therapy.
Who Performed the Research and Where Was it Presented:
Dr. Nitin Jain from The University of Texas MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have a dysfunctional immune system, and researchers have been investigating therapies that potentially enhance the immune response. T cells have checkpoint proteins on their surface, which keep immune responses from being too strong, but they can also prevent T cells from killing cancer cells. Checkpoint inhibitors are a class of drugs that block checkpoint proteins, allowing T cells to kill cancer cells. For this study, researchers wanted to determine whether combining the checkpoint inhibitor atezolizumab with venetoclax and obinutuzumab would be an effective first-line therapy for patients with CLL.
Methods and Participants:
This is a phase 2 clinical trial of atezolizumab-venetoclax-obinutuzumab in patients with previously untreated CLL. Treatment lasted for 14 cycles, or slightly over one year.
Results:
- Thus far, 37 patients have enrolled in the study, and the median follow-up time is a bit over three years (40 months).
- Among the 31 patients who completed treatment through cycle 14, 97% had undetectable measurable residual disease (uMRD) in the bone marrow.
- Approximately 17% of patients experienced MRD relapse after a median time of one year, but none have required subsequent CLL therapy as of yet.
- Progression-free survival estimates are 94% at two years and 89% at four years.
- One of the known issues with checkpoint inhibitors is that they can cause too much activation of the immune system, which can lead to inflammation of different organs, including the liver, colon, and lungs.
- Three patients discontinued atezolizumab early due to immune-related side effects.
- Moderately to severely low neutrophil counts occurred in 59% of patients.
- Sophisticated testing revealed better functioning CD8 T cells in the responders vs. non-responders.
Conclusions:
The combination atezolizumab-venetoclax-obinutuzumab produced high rates of remission as a frontline CLL therapy. However, it probably would not be a go-to choice for first therapy because it can cause serious immune side effects, and there are already several other very good options available for patients with treatment-naïve CLL. This combination is more promising as a treatment for Richter transformation.
It is important for patients to remember that adding another drug isn’t always better. Sometimes, adding a drug to an already good combination doesn’t always improve efficacy. In other cases, it can improve efficacy a little bit, but it can also really increase side effects and toxicities.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract: Atezolizumab Combined with Venetoclax and Obinutuzumab for Frontline CLL
