Site Editor
Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Tuesday, January 21, 2025
An investigator-initiated phase II trial conducted by Patrick K. Reville, MD, MPH, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues explored the synergistic effects of the combination of the immune checkpoint inhibitor atezolizumab, the BCL2 inhibitor venetoclax, and the monoclonal antibody obinutuzumab in patients with untreated chronic lymphocytic leukemia (CLL). Their findings, which were presented during the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1014), also revealed potential mediators of immune checkpoint blockade response.
A total of 37 patients were enrolled and administered the triplet regimen. Of those who completed 14 cycles of treatment (n = 31), 30 had undetectable measurable residual disease (MRD) in the bone marrow at a sensitivity of 10-4 cells, and 1 had low MRD positivity. Five of those who achieved an MRD-undetectable status experienced a relapse at a median of 12.2 months after completing therapy. The estimated 2- and 4-year progression-free survival rates were 94% and 89%, respectively. For overall survival, the estimate was 94% at both time points.
Three patients discontinued treatment with atezolizumab because of immune-related adverse events. More than half of the enrolled population (59%) experienced grade 3 or 4 neutropenia. Thrombocytopenia of grade 3 or 4 was documented in 32% of patients.
Six patients with paired bone marrow samples were selected for correlative single-cell RNA sequencing analyses; the subset equally comprised early responders and nonresponders. Differential abundance analyses revealed a CD8-positive T-cell cluster enriched with high expression of NR4A2 and TOX in responders and nonresponders, respectively. Using gene-set enrichment analyses, the investigators identified tumor necrosis factor–alpha signaling pathways strongly enriched in responding T and natural killer cells. Immune repertoire analyses showed increased T-cell receptor expansions and transitions in responders. Cell-cell interaction predictions revealed higher interactions between CLL cells and immune cells in responders, with enriched antigen presentation pathways in responding monocytes.
Disclosure: Dr. Reville reported no conflicts of interest. For full disclosures of the other study authors, visit ash.confex.com.
2024 ASH Annual Meeting & Exposition
JNCCN Spotlights
Resources
For your Patients
