Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML
Menée sur 423 patients traités à l'aide d'imatinib pour une leucémie myéloïde chronique, cette étude identifie deux facteurs (réponse moléculaire précoce et sexe féminin) associés au critère d'interruption du traitement défini par l'essai CML8 (BCR-ABL1 indétectable pendant deux ans)
Recent studies have demonstrated that some CML patients can maintain remission after imatinib discontinuation. A prerequisite is stable undetectable BCR-ABL1. It is not known how many patients achieve this response or the factors associated with its achievement. We examined 423 de-novo imatinib-treated patients to determine the cumulative incidence of achieving the discontinuation criteria as defined in the CML8 study (≥2 years undetectable BCR-ABL1 [Stable MR4.5]), and predictive factors. After 8 years of imatinib, the cumulative incidence of Stable MR4.5 was 36.5%. Therefore, 9-15% of first-line imatinib-treated patients would maintain remission after discontinuation. The BCR-ABL1 level at 3 months and factors at diagnosis were examined for association with Stable MR4.5: Sokal risk, age, sex, and assigned imatinib dose. The only independent predictors were female sex (54.4% versus 27.2%; P=.018) and the 3 month BCR-ABL1; P<0.001. The highest cumulative incidence of Stable MR4.5 after 8 years was 78.2% for patients with BCR-ABL1 ≤0.10%IS at 3 months (n=38). Time to major molecular response (MMR) influenced the time to reach Stable MR4.5 (P<.001), suggesting slower dynamics of response with delayed MMR. The findings justify the focus on rapid reduction of BCR-ABL1 as a strategy to maximize potential suitability for imatinib discontinuation studies. Iris trial registered at http://www.clinicaltrials.gov as NCT00006343; Tops trial registered at http://www.clinicaltrials.gov as NCT00124748; Tidel I trial registered at www.ANZCTR.org.au as ACTRN12607000614493; Tidel II trial registered at www.ANZCTR.org.au as ACTRN12607000325404
Blood , résumé, 2013