Discontinuation of Imatinib Therapy After Achieving a Molecular Response in Chronic Myeloid Leukemia Patients.

Imatinib (IM) has greatly improved survival rates in chronic myeloid leukemia* (*CML). However, all patients (pts) must continue treatment for an unknown period of time.

A pilot study of the first pts who discontinued IM therapy was previously reported (Rousselot et al. Blood 2007;109:58–60). The multicentre study Stop Imatinib (STIM) was initiated in July 2007 in order to evaluate the persistence of complete molecular remission (CMR) after stopping IM, and to determine the factors that could be associated with CMR persistence.

Inclusion criteria were IM treatment duration of at least 3 years and sustained CMR. Sustained CMR was defined as BCR-ABL/ABL levels below a detection threshold corresponding to a 5-log reduction (undetectable signal using RQ-PCR) for at least 2 years. Molecular relapse, defined as RQ-PCR positivity, was taken into account if confirmed in two successive assessments. In cases of molecular relapse, pts were re-challenged with IM at 400 mg daily.

From the pilot study, 8 among 15 patients are still in CMR with a median follow up of 42 months (range 37-49). The number of patients enrolled in the STIM study was 69. 34 patients had received interferon alpha (IFNa) prior to IM and 35 pts were de novo. Median follow-up (range) was 17 months (6-24). 37 pts relapsed (loss of CMR) within the first 6 months and two patient relapsed after more than 6 months (M7 ,M18). At M12, the probability of remaining in CMR was 45% (95% CI: 33-56%). For previously treated with IFN (n=34) this probability was 44% (95% CI: 27-59%) versus 46% (95% CI: 29-61%) for de novo pts (p=0.93, overall). All patients in molecular relapse were sensitive again after imatinib re-challenge (decreasing BCR-ABL level, achievement CMR again). Male pts 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 cells counts prior to IM discontinuation were significantly lower in relapse pts (mainly cytotoxic cells CD56dim) as compared to the non relapse pts(p=0.005).

We have confirmed that CMR can be sustained after discontinuation of imatinib with a long follow-up, particularly in male patients and in pts 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.

(ClinicalTrials.gov number, NCT00478985 [ClinicalTrials.gov])

Mahon:Amgen: Honoraria; Novartis Pharma: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria. Guilhot:Novartis Pharma: Consultancy, Honoraria; BMS: Consultancy, Honoraria.