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

Abstract

Key Points• Independent predictors of stable, undetectable BCR-ABL1 during first-line imatinib therapy were female sex and the BCR-ABL1 value at 3 months.• Time to achieve an MMR influenced time to stable, undetectable BCR-ABL1, suggesting slower dynamics of BCR-ABL1 decline with delayed MMR.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 MR 4.5 ]), and predictive factors. After 8 years of imatinib, the cumulative incidence of Stable MR 4.5 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 MR 4.5

The clinical significance of patients' sex in chronic lymphocytic leukemia

“…27 Another recent report, in chronic myeloid leukemia, included female sex as one of the two more significant predictors of stable molecular response after long-term imatinib therapy. 28 Another observation in our study is that the proportion of males is higher in patients requiring treatment than in patients with earlier stage disease and hence is reflected in most clinical trials ( Table 6). As in our registration series, the male:female ratios are lower in observational series of Binet stage A or Rai stage 0.…”

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when is this a safe option to consider?

“…Factors associated with longer TFR include prior IFN therapy before TKI therapy, longer duration of CMR before discontinuation, and longer duration of IM use before discontinuation (Ͼ 60 months). 12,13,15,39,40 In addition, achievement of an early deep molecular response at 3 months is associated with durable deep molecular response. [40][41][42] It is unknown at this time if second-generation TKIs result in an increased probability of TFR.…”

“…12,13,15,39,40 In addition, achievement of an early deep molecular response at 3 months is associated with durable deep molecular response. [40][41][42] It is unknown at this time if second-generation TKIs result in an increased probability of TFR. However, the 2 case series in Table 2 and the study by Rea et al in Table 1 report results that appear superior to IM-treated patients.…”

“…[23][24][25][26] Three seemingly relevant ASH abstracts were eliminated because either an updated abstract was available 27,28 or a more in-depth manuscript had been published with the data from the abstract. 29 One abstract from the 2012 (no. 0189) and one from the 2013 (no.…”

Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: Importance of achieving treatment‐free remission

“…Mahon and colleagues estimated that 10% of patients with CML are eligible for attempting TFR following sustained molecular remission on imatinib, approximately 40% of whom would remain in molecular remission after imatinib cessation [45]. Similarly, an analysis of several clinical studies of patients treated with frontline imatinib estimated that, based on the cumulative rate of MR 4.5 of patients treated with imatinib for 8 years and published data, only 9% to 15% of patients would maintain stable molecular remission following treatment cessation [53]. Treatment with nilotinib and dasatinib, both of which induce deeper and sustained molecular responses compared with imatinib [16,17], may enable a higher number of patients to achieve the sustained deeper remissions required for enrollment in TFR studies.…”