Complete Molecular Remission can be Sustained in CML After Discontinuation of Imatinib, Research Concludes
Complete molecular remission (CMR) can be sustained in chronic myeloid leukemia (CML) after discontinuation of imatinib (IM) with a long follow-up, particularly in male patients and in patients with cytotoxic NK cells in their peripheral blood. That was among the results of a trial presented at the 51st Annual Meeting and Exposition of the American Society of Hematology in New Orleans.
French researchers conducted an extension of a multicenter study, Stop Imatinib (STIM) begun in July 2007 in order to evaluate the persistence of CMR after stopping IM and to determine the factors that could be associated with CMR persistence. Imatinib has greatly improved survival rates in CML. Inclusion criteria were IM treatment duration of at least three years and sustained CMR (defined as BCR-ABL/ABL levels below a detection threshold corresponding to a five-log reduction [undetectable signal using RQ-PCR] for at least two years. Molecular relapse, defined as RQ-PCR positivity, was taken into account if confirmed in two successive assessments. In cases of molecular relapse, patients were rechallenged with IM at 400 mg daily.
The number of patients enrolled in the pilot study was 69; of that group, 34 had received interferon alpha (IFNa) prior to IM and 35 patients were de novo. Median follow-up was 17 months (range 6-24). Thirty-seven patients relapsed (loss of CMR) within the first six months and two relapsed after more than six months (months 7 and 18). At month 12, the probability of remaining in CMR was 45% (95% confidence interval [CI], 33% to 56%). With patients previously treated with IFNa, (n=34) this probability was 44% (95% CI, 27 to 59%) vs 46% (95% CI, 29% to 61%) for de novo patients (P=0.93, overall). All patients in molecular relapse were sensitive again after imatinib rechallenge (decreasing BCR-ABL level, achieving CMR again). Male patients had a better probability of survival without molecular relapse (P>=0.02) and a trend was observed for the low Sokal risk group (P= 0.06). Peripheral NK cell counts prior to IM discontinuation were significantly lower in relapse patients (mainly cytotoxic cells CD56dim) as compared with the non-relapse patients (P=0.005).
According to the researchers, they have confirmed that CMR can be sustained after discontinuation of imatinib with a long followup, particularly in male patients and in those with cytotoxic NK cells in their peripheral blood. Using stringent criteria, it is possible to stop treatment in patients with sustained CMR, even in those treated with IM as a single agent, they conclude.