Cellular Therapy in Chronic Lymphocytic Leukemia: Have We Advanced in the Last Decade?

Abstract

Background: Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell malignancy, affecting mainly older adults. Despite the recent introduction of multiple targeted agents, CLL remains an incurable disease. Cellular therapy is a promptly evolving area that has developed over the last decades from such standard of care as hematopoietic cell transplantation (HCT) to the novel treatment modalities employing genetically engineered immune cells. Summary: Tailoring the proper treatment for each patient is warranted and should take into account the disease biology, patient characteristics and the available treatment modalities. Nowadays, the most broadly applied cellular therapies for CLL management are HCT and chimeric antigen receptor-T (CAR-T) cells. However, CAR-T cell therapy is currently not yet approved in CLL and the appropriate sequencing for the administration of these agents remains to be clarified. Key Messages: The current review will discuss various available cellular treatment options, their advances and limitations as well as the optimal timing for the employment of such therapies in CLL patients.

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

“…Within the category of high-risk patients, two distinct groups can be identified: high-risk I, characterized by clinically resistant disease to CIT with TP53 aberrations but a positive response to signaling pathway inhibitors, and high-risk II, marked by disease resistance to both CIT and signaling pathway inhibitors. In cases where resistance to BTKi and/or BCL-2 is observed, alloHCT could be a viable alternative, especially when therapeutic options are limited [ 144 ].…”

Broadening the horizon: potential applications of CAR-T cells beyond current indications

“…Engineered γδ-T cells have further been shown to impact the TME and potentially show lower rates of on-target-off-tumor effects ( 250 ). Donor-derived γδ-T cells could be another therapeutic option as they exhibit natural anti-tumor activity ( 251 ). Another aspect of fine-tuning γδ-T cells for antitumor use includes the specific expression of chemokines like IL-15 to increase longevity and tumor control ( 252 ).…”