Discontinuation of Second-Line Dasatinib Feasible in CML


Many chronic myeloid leukemia patients who discontinue second-line dasatinib maintain a deep molecular response, according to a new study.

Many chronic myeloid leukemia (CML) patients who discontinue second-line dasatinib, a tyrosine kinase inhibitor (TKI), maintain a deep molecular response, according to a new study. Those who lost the deep response regained it quickly when the drug was administered again.

Previous research has shown that discontinuing the TKI imatinib after a deep response is feasible in many CML patients. “A high proportion of patients who had inadequate response to imatinib responded to dasatinib therapy and, therefore, we speculated that dasatinib could be successfully discontinued after a shorter period of confirmed deep molecular response than for imatinib,” wrote study authors led by Jun Imagawa, MD, of Hiroshima University in Japan.

The new study was a prospective study; it enrolled 88 patients in a dasatinib consolidation phase, and 25 of those were excluded due to either fluctuations in BCR-ABL1 transcript levels or positive expression of major and minor BCR-ABL1 transcripts in CML cells. Thus, 63 patients who had a deep molecular response after at least 1 year on dasatinib then discontinued the drug and were included in the analysis. The results were published online ahead of print in Lancet Haematology.

After a median follow-up period of 20 months, 30 patients maintained the deep molecular response. The other 33 had molecular relapses, all of which occurred within the first 7 months after dasatinib discontinuation (median 3 months). At 6 months, the probability of treatment-free remission was 49%; at 12 months, it was 48%.

In those patients who did have a molecular relapse, dasatinib was restarted in all but one, who chose to receive nilotinib instead. In all 33 patients, rapid molecular response was observed after treatment was restarted. Twenty-nine patients (88%) returned to a deep molecular response within 3 months of treatment restart, and the other four patients regained deep molecular response by 6 months.

One patient did lose deep molecular response again at 12 months, but the authors noted that the BCR-ABL1 transcript level was low (0.0086%) in this patient. There were no cases of progression to advanced-phase disease.

“The properties of second-generation TKIs might mean the treatment duration can be shortened for other drugs, and raises the possibility of drug-free remission, which could lead to improved long-term quality of life and reductions to medical expenses,” the authors wrote. They noted that patients who initially started dasatinib treatment because of resistance to imatinib had worse outcomes than those who were not resistant.

The authors have begun a second study testing discontinuation of first-line dasatinib in CML patients, after at least 3 years of treatment.

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