Chronic lymphocytic leukemia (CLL) is characterized by a dysregulated immune system and the clinical course of CLL is dominated by events associated with immune dysfunction including increased susceptibility to infection related to hypogammaglobulinemia (low levels of gammaglobulin in the blood), impaired T cell, NK cell and neutrophil function and poor responses to vaccinations. A confounding contrast to the above is the autoimmune issues that also plague CLL patients.
At the April 2015 CLL Patient Education and Empowerment meeting held in conjunction with the CLL Research Consortium meeting at UCSD in San Diego, Dr. John Gribben from Saint Bartholomew’s Hospital and Queen Mary’s School of Medicine at the University of London provided a very clear description of the impact on the immune system in CLL, as well as the strategies that are currently used, and are in development to fight this disease.
Malignant B cells have evolved very effective ways to prevent immune attack by the T-cells. Somehow contact with the malignant B-cell creates defects in the T-cells. It’s necessary to understand how CLL cells do this to be able to overcome these defects and to turn the immune system back on. Strategies that are currently employed and are in development include:
- Allogeneic stem cell transplantation
- Immunomodulatory drugs – lenalidomide, CC-122
- Blockade of inhibitory “checkpoint” signals eg. PD1/PDL1
- Generation of tumor specific T-cell responses – bispecific antibodies, small molecules
- Ex-vivo modification of T-cells
- Gene modification
Dr. Gribben also reviewed the current consensus criteria for considering allogeneic stem cell transplant for CLL patients, including the data that supports those criteria. Other factors to consider include:
- Disease risk
- Donor availability
- Patient’s suitability based on age, frailty, comorbidities and patient preference
In the context of the new targeted drugs that are now available, these factors should probably be reconsidered.
Using some terrific cartoon graphics, Dr. Gribben reviewed the various immune responses that take place as our own immune system attempts to destroy the CLL cells, as well as a great illustration of how CAR-T attacks the CLL cells.
Future directions for immune strategies to treat CLL would include:
- Refining the role of allogeneic stem cell transplant (if any) in the era of novel targeted therapies
- Target CLL specific antigens
- Improve CAR-T approaches
- Clinical trials to study checkpoint inhibitors in CLL
Here is Dr. Gribben’s lecture. Enjoy!
Betsy Dennison, RN 11/22/15