Discontinuing Tyrosine Kinase Inhibitors can Improve Outcomes in Leukemia Patients

Discontinuing Tyrosine Kinase inhibitor (TKI) is safe in patients suffering from chronic myeloid leukemia (CML). This has shown better patient reported outcomes. CML is a cancer of the white blood cells. It is characterized by increased and unregulated growth of the myeloid cells (blood forming cells) in the bone marrow. These cells accumulate in the blood. Tyrosine Kinase Inhibitors (TKI) are the drugs that inhibit tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by phosphorylation. TKI inhibits the activation of these proteins. Tyrosine kinases are a part of many cell functions including cell signaling, growth and division. These enzymes are very active and functional in patients suffering from a number of cancer. They are a type of targeted therapy for cancer.

Dr. Ehab Atallah of the Medical College of Wisconsin in Milwaukee commented, " Consider treatment discontinuation in CML patients who have achieved a sustained deep molecular response. After treatment discontinuation, close monitoring with BCR-ABL PCR is necessary. PCR need to be monitored monthly for six months, every two months for 18 months then every three months thereafter.Patients with undetectable BCR-ABL1 at the time of discontinuation and at three months have a 96% of staying in major molecular response and not restarting therapy. "

Droplet Digital PCR (ddPCR) is a method for performing digital Polymerase Chain Reaction that is based on water-oil emulsion droplet technology. PCR amplifies the molecules present in the droplet.

172 CML patients were enrolled for this trial. The average age of these patients was 60 years and 52 % participants were women. This study was conducted across 14 centers in US from 2014-2016. These patients had chronic disease and were well controlled on TKI ( examples: imatinib, dasatinib, milotinib or bosutinib).

Out of 171 patients, 112 patients stayed in a major molecular response and 104 achieved treatment free remission (TFR). Of the 112 patients in TFR at 12 months observed clinically significant improvements in fatigue (80.4%), depression (34.8%), diarrhea (87.5%), sleep disturbance (21.4%), and pain interference (4.5%). The most important point to be noted is that restarting TKI worsened primary outcomes, patient-reported outcomes (PROSs).

Dr.Atallah noted, " ddPCR is not widely available at this point. I think it should be more widely available to help guide and inform treatment discontinuation decisions."

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Dr. Theodore Braun of Oregon Health and Science University in Portland, coauthor of a related editorial, commented,” This adds to an already large body of evidence that TKI discontinuation in patients with a deep molecular response is extremely safe. This is the first study to demonstrate patient-reported outcomes after TKI discontinuation demonstrates that patients do indeed have improved quality of life after discontinuation.Regarding biomarkers for successful discontinuation, all study participants had less than one leukemia cell in ten thousand normal cells "

Studies were conducted previously on this population. 50% of such patients did not have disease relapse upon TKI discontinuation.

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Apart from this there are no studies that show the biomarker that can predict the relapse. DdPCR may be useful in this case but still there is research going on the same.

Source-Medindia