Better Strategies for the Treatment of High-Risk Chronic Lymphocytic Leukemia

In season 3, episode 4 of Targeted Talks, Alexey Danilov, MD, PhD, associate director, Toni Stephenson Lymphoma Center, and professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, discusses the shift toward utilizing cellular therapy to treat high-risk patients with chronic lymphocytic leukemia (CLL).

The definition of high-risk has changed in CLL based on the emergence of better therapies. Today, patients with tp53 mutations, complex karyotype, and patients who have progressed while on targeted therapies are considered to be high risk.

Historically for the high-risk CLL population, allogeneic stem cell transplant and chemoimmunotherapy were the standards of care. The treatment landscape has since expanded to include Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. These newer drug classes can be used sequentially and in the clinical trial setting, they are being investigated as combinations. PI3K inhibitors are also available and effective for the treatment of high-risk CLL.

The role of transplant is after patients progress on available targeted therapies.

In terms of cellular therapies have been another positive development for high-risk CLL, says Danilov. In studies, responses to chimeric antigen receptor (CAR) T-cell therapy have been observed in patients with deletion 17p and those who are refractory to BTK inhibitors. The next step with CAR T cells is understanding the durability of response and learning better ways to handle severe toxicities like cytokine release syndrome.

The latest treatment strategies being investigated for high-risk CLL include CAR T-cell therapy combined with targeted therapies, novel BTK inhibitors for BTK-refractory patients, and natural killer cells, explains Danilov.