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treatment-free survival is shown in Figure 1A. The estimat- ed 3-year treatment-free survival was 62.8%. Among patients with a confirmed loss of MR4.5, 25 patients lost the MR4.5 within the first 6 months after discontinuing nilotinib (median, 3.4 months; range, 1.8–5.8 months), and the remaining four patients lost the MR4.5 between 16 and 20 months within the TFR phase (Figure 1B).
In a subanalysis of groups based on prior TKI before entry into the STAT2 trial, the 12-month TFR rate was 62.5% (95% CI: 45.8–77.3%) in the ‘imatinib only’ group and 69.7% (95% CI: 51.3–84.4%) in the ‘nilotinib follow- ing imatinib’ group. In another subanalysis based on posi- tivity of molecular residual disease (MRD) before the TFR phase, the 12-month TFR rate was 56.8% (95% CI: 39.5–
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72.9%) in the MRD group and 78.0% (95% CI: 62.4– 89.4%) in the UMRD with MR5 group; the corresponding 24-month TFR rates were 48.6% (95% CI: 31.9–65.6%) and 75.6% (95% CI: 59.7–87.6%).
An analysis of baseline factors as predictors of TFR at 12 months was conducted. With the exception of detectable MRD before entering the TFR phase (odds ratio, 0.369; 95% CI: 0.138–0.988; P=0.0473), there were no significant predictors in the univariate logistic regression analysis, including the absolute number of natural killer cells and natural killer cell cytotoxicity (Table 3). Multivariate analy- sis was not, therefore, performed. On the other hand, the treatment-free survival curve was significantly better in the UMRD with MR5 group than in the MRD group (estimated
Figure 1. Treatment-free remission after 2-year consolidation with nilotinib. (A) Kaplan-Meier estimates of treatment-free survival after discontinuation of nilotinib (n=78). (B) The kinetics of BCR-ABL1 transcripts in the treatment-free remission (TFR) phase. Twenty-five patients lost MR4.5 within 12 months and eight patients showed fluctuations in the amounts of BCR-ABL1 transcript around the MR4.5 level. Among the eight patients with fluctuations, four lost MR4.5 after 16, 16, 17, and 20 months. (C) Kaplan-Meier estimates of treatment-free survival after discontinuation of nilotinib according to the molecular response [molecular residual disease (MRD) positive or undetectable MRD (UMRD with MR5)] at enrollment in the TFR phase. UMRD with MR5 was defined as undetectable BCR-ABL1 transcripts by IS-PCR in which at least 100,000 control genes (ABL1) were required for the sensitivity of MR5. (D) Cumulative incidence of MR4.5 in patients who lost MR4.5 during the TFR phase and were subsequently readministered nilotinib (n=29). (E) Cumulative incidence of reacquisition of major molecular response (MMR) in patients who lost MMR and were readministered nilotinib (n=16).
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haematologica | 2018; 103(11)