Co-author(s)
Cony-Makhoul,
P, Hôpital d'Annecy, Annecy, France
Réa, D, Hôpital Saint-Louis, Paris, France
Legros, L, Hôpital Larchet, Nice, France
Tulliez, M, Hôpital Henri Mondor, Créteil, France
Roy, L, Hôpital de Poitiers, Poitiers, France
Charbonnier, A, Institut Paoli Calmettes, Marseilles, France
Guilhot, F, Inserm CIC 802 CHU de Poitiers, Poitiers, France
Mahon, FX, INSERM U876, Université Victor Segalen, Bordeaux, France
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- Background.
We have reported the results of imatinib discontinuation in 100 CML (Chronic
Myelogenous Leukemia) patients in complete molecular response (CMR) for more
than 2 years under imatinib therapy (STIM study). The molecular relapse was
defined by two consecutive positive values of the BCR-ABL/ABL ratio. Using
this criterion, 59% of the patients had to restart imatinib therapy and
achieved a second CMR (Mahon et al. Lancet Oncology 2010). However, we
identified patients experiencing occasional positive values without a
confirmed molecular relapse. We then asked whether the loss of major
molecular response (MMR) could be a more accurate criterion for restarting
imatinib in an independent cohort of patients.
Patients and methods. Patients were retrospectively analysed. CP-CML patients
were eligible if they were in CMR (CMR 4.5 log) under imatinib therapy for
more than 2 years. Those patients were not enrolled in the STIM study because
the study was not initiated or closed or because they experienced one
positive value of the BCR-ABL/ABL ratio during the 2 years follow-up. The
criterion for restarting imatinib was the loss of MMR. We were then able to
calculate molecular relapse free survival using different end-points such as
loss of CMR (only one BCR-ABL positivity), loss of CMR using the STIM
definition and loss of MMR.
Results. 25 CP-CML patients were included in the analysis. Median follow-up
is 54.8 months (33-102.7). Sex ratio (M/F) was 53% with a median age of 55.7
years (32.7-76.7). Sokal score distribution was 39.1%, 34.7% and 26% for low,
intermediate and high values respectively. 14 out of 25 patients received
interferon therapy prior to imatinib. Median duration of imatinib therapy and
median duration of CMR prior to discontinuation was 58.7 months (30.1-117.6)
and 33.2 months (13.6-72.8). One patient had a CMR duration less than 24
months. 11 out of 25 patients (44%) had a least one BCR-ABL positive value
after the achievement of CMR. 9 patients (36%) restarted imatinib including 7
patients after the loss of MMR and two patients after the loss of CMR (these
two patients were censored at the time of treatment initiation for the loss
of MMR analysis). We next compared different end-points in order to evaluate
the best criterion for restarting imatinib after discontinuation. Median
relapse free survival was 4.8 months, 13.7 months and not reached using loss
of CMR, loss of CMR according to the STIM study and loss of MMR criteria
(p=0.035). At 48 months, 32%, 40,9% and 78.7% of the patients were relapse
free using the same criteria respectively. Of note, among the 18 patients
experiencing a persistent MMR after imatinib discontinuation, 7 (38.9%) lost
their CMR according the STIM criteria and did not restart imatinib.
Conclusions. Using the loss of MMR, 78.7% of the patients are relapse free
(and treatment free) at 48 months following imatinib discontinuation. We were
able to identify patients with long lasting MMR despite a loss of CMR
suggesting that a proportion of these patients were able to control their
tumour burden without the need of imatinib therapy.
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