Dasatinib discontinuation after 1 Year possible in some CML patients

Blood cancers

By Nicola Garrett

20 Nov 2015

Second-line dasatinib can be discontinued in patients with chronic myeloid leukaemia after they have sustained deep molecular response for more than 1 year, a study suggests.

Writing in the Lancet Haematology the researchers said most haematologists think that patients should have achieved sustained deep molecular response for at least 2 years before imatinib treatment is stopped.

“Dasatinib, however, is more potent than imatinib and might be stopped safely after a shorter duration of sustained deep molecular response,” they wrote.

The prospective multicentre study from Japan involved 88 patients who received dasatinib consolidation therapy with confirmed deep molecular response for at least 1 year.

Of those, 63 discontinued therapy and were followed up with every month in year 1, every 3 months in year 2, and every 6 months in year 3 to assess deep molecular response and immunological profiles.

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% and 48% at 12 months.

Treatment was restarted in the 33 patients with relapse; rapid molecular responses were seen in all 33 patients, of whom 29 (88%) regained deep molecular response within 3 months, as did the remaining four by 6 months.

The proportion of patients who remained in treatment-free remission was notably poorer among those who switched to dasatinib because of imatinib resistance (8%) than in other patients (58%) the study authors noted.

“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,” they concluded.

The results, however, needed to be compared with forthcoming studies in which dasatinib is stopped after longer periods of deep molecular response, such as 2 years, to identify the optimum period, they added.

In an accompanying editorial  haematologist Dr David Ross from SA Pathology in Adelaide said the most intriguing findings from the trial related to the quantification of immune cell subsets before dasatinib was stopped.

In the study the researchers found that high natural-killer cells (NK-cell) and low δγ+ T-cell and CD4+ regulatory T-cell (CD25+ CD127low) counts significantly correlated with sustained discontinuation.

The function of γδ+ T cells was complex, but the overall pattern points to an immune effector phenotype reducing the risk of molecular recurrence, Dr Ross said.

But the real relevance of NK cell numbers in predicting treatment-free remission after treatment with TKIs for chronic myeloid leukaemia remained unclear.

“Whether cell counts are associated with some other disease- related or immunological parameter, or whether they have a crucial functional role in treatment-free remission should be answered in future studies,” he said.

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