Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML

Yeung1,2,4, David M. Ross2,4,5, Jodi A. Prime1, Chani R. Field1, Haley K. Altamura1, Alexandra L. Yeoman1, Jasmina Georgievski1, Bronte A. Jamison1, Stuart Phillis1, Brad Sullivan1, Nancy E. Briggs6, Mark Hertzberg7,8, John F. Seymour7,9, John Reynolds10, and Timothy P. Hughes2,4,7
+ Author Affiliations

Key Points

1. Independent predictors of stable, undetectable BCR-ABL1 during first-line imatinib therapy were female sex and the BCR-ABL1 value at 3 months.

2. Time to achieve an MMR influenced time to stable, undetectable BCR-ABL1, suggesting slower dynamics of BCR-ABL1 decline with delayed MMR.

Abstract

Recent studies have demonstrated that some patients with chronic myeloid leukemia (CML) can maintain remission after discontinuation of imatinib. 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 of 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% to 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% vs 27.2%; P = .018) and the 3-month BCR-ABL1 (P < .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 a delayed MMR. The findings justify the focus on rapid reduction of BCR-ABL1 as a strategy to maximize potential suitability for imatinib discontinuation studies. The Iris trial was registered at http://www.clinicaltrials.gov as NCT00006343. The Tops trial was registered at http://www.clinicaltrials.gov as NCT00124748. The TIDEL I trial was registered at www.ANZCTR.org.au as ACTRN12607000614493. The TIDEL II trial was registered at www.ANZCTR.org.au as ACTRN12607000325404.

http://bloodjournal.hematologylibrary.org/content/121/19/3818.full