Arnon Kater, MD, PhD, Professor of Internal Medicine in the Faculty of Medicine at the University of Amsterdam (AMC-UvA), gives an overview of the chronic lymphocytic leukemia (CLL) landscape and discusses the GLOW trial.

CLL is a rare blood cancer resulting in a build-up of lymphocytes in bone marrow, lymph nodes, and blood. The disease is considered treatable, but relapse is very common. Furthermore, many CLL patients cannot withstand the intensive chemotherapy needed to bring them into complete remission.

As Dr. Kater explains, it is common for CLL patients to develop autoimmune complications such as autoimmune neutropenia and autoimmune hemolytic anemia. The treatment landscape for CLL has shifted from chemotherapy to chemoimmunotherapy and now targeted treatments. The targeted treatments tend to fall into one of two categories: PTK inhibitors (e.g., ibrutinib) and BCL-2 inhibitors (eg., venetoclax). As Dr. Kater explains, CLL malignant cells move between the blood and the lymph nodes. In the blood, these cells are more vulnerable and depend on BCL-2 to avoid spontaneous apoptosis. BCL-2 inhibitors have been shown to effectively drive cells into apoptosis. In the lymph nodes,  CLL malignant cells are more resistant to apoptosis. PTK inhibitors work by preventing these cells from entering the lymph nodes. Combining PTK inhibitors with BCL-2 inhibitors thus forces these cells to remain in the blood where they cannot gain further protection.

GLOW (NCT03462719) was a phase 3 clinical trial which assessed progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+V) compared with chlorambucil plus obinutuzumab (C+O) in elderly or unfit patients with CLL. The study met its primary endpoint of superior progression-free survival (PFS), demonstrating a reduction in the risk of disease progression or death for I+V of approximately 78% compared to C+O. 

Secondary endpoints included rates of undetectable minimal residual disease (uMRD), complete response rate (CR) and overall response rate (ORR). The rate of uMRD in the bone marrow was significantly higher for patients treated with I+V compared to those treated with C+O. Three months after the completion of treatment uMRD was observed in 51.9% and 17.1%, respectively. Peripheral blood (PB) uMRD persisted 12 months after the end of treatment in 49% with I+V and 12% with C+O. The CR rate was also significantly higher with I+V vs. C+O (38.7% vs. 11.4%). The ORR was not significantly different between I+V and C+O treated groups. Time to subsequent therapy was longer for I+V.

For more information about CLL and other rare cancers, visit checkrare.com/diseases/cancers/