Advertisement

Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study

Delphine Rea, Franck E. Nicolini, Michel Tulliez, François Guilhot, Joelle Guilhot, Agnès Guerci-Bresler, Martine Gardembas, Valérie Coiteux, Gaelle Guillerm, Laurence Legros, Gabriel Etienne, Jean-Michel Pignon, Bruno Villemagne, Martine Escoffre-Barbe, Jean-Christophe Ianotto, Aude Charbonnier, Hyacinthe Johnson-Ansah, Marie-Pierre Noel, Philippe Rousselot, François-Xavier Mahon and for the France Intergroupe des Leucémies Myéloïdes Chroniques

Article Figures & Data

Figures

  • Figure 1.

    Molecular relapses and TFR after 2G-TKI discontinuation. (A) Evolution of BCR-ABL1 transcripts over time as measured by RT-qPCR from 2G-TKI discontinuation until MMR loss in relapsing patients (n = 26). Red lines correspond to molecular relapses occurring within 12 months after treatment cessation, and blue lines to relapses occurring after 12 months. (B) Cumulative incidence of molecular relapses. (C) Treatment-free remission.

  • Figure 2.

    Evolution of BCR-ABL1 transcript levels from molecular relapse onward. (A) BCR-ABL1 transcript levels as measured by RT-qPCR at molecular relapse and at treatment resumption in patients with available evaluations at both time points (n=13). Horizontal bars represent median, minimum, and maximum values. (B) BCR-ABL1 transcript levels as measured by RT-qPCR at molecular relapse and every 3 months until 12 months after treatment resumption (n=25). One patient could not be evaluated after molecular relapse because of death unrelated to CML, and 1 patient had not yet been evaluated at 12 months. Solid dots correspond to detectable BCR-ABL1 transcripts. Open dots correspond to undetectable BCR-ABL1 transcripts.

  • Figure 3.

    Landmark analysis according to molecular response categories in patients with MMR 3 months after 2G-TKI discontinuation. (A) Cumulative incidence of relapse and overall P value (Gray’s test) are shown. (B) TFR and overall P value (log rank) are shown.

  • Figure 4.

    Outcome after 2G-TKI discontinuation according to prior suboptimal response or TKI resistance. (A) Cumulative incidence of relapse and overall P value (Gray’s test) are shown. (B) TFR and overall P value (log rank) are shown.

Tables

  • Table 1.

    Baseline characteristics of patients

    ParametersResults (n=60)
    Demographics
     Median age60 y (range: 26-81)
     Female gender63.3% (n = 38)
    CML at diagnosis
     Chronic phase100% (n = 60)
     Sokal risk group
      Low53.3% (n = 32)
      Intermediate26.7% (n = 16)
      High15% (n = 9)
      Unknown5% (n = 3)
     Cytogenetics
      Ph1 without ACAs93.2% (n = 56)
      Ph1 with ACAs3.4% (n = 2)
      Unknown3.4% (n = 2)
     M-bcr transcript type100% (n = 60)
    Treatment history
     Prior IFN-α28.3% (n = 17)
     1st line dasatinib or nilotinib13.3% (n = 8)
     2nd line dasatinib or nilotinib66.7% (n = 40)
     3rd line dasatinib or nilotinib20% (n = 12)
     Intolerance to imatinib65% (n = 39)
     Suboptimal response or resistance to imatinib21.7% (n = 13)
      Imatinib-resistant BCR-ABL1 mutation*30.8% (n = 4)
       No mutation53.8% (n = 7)
       Mutation status unknown15.4% (n = 2)
     Median duration of TKI therapy76 mo (range: 36-153)
     Median duration of 2G-TKI treatment39 mo (range: 19-83)
     Median duration of uMR4.529 mo (range: 24-64)
    Treatment discontinuation
     Dasatinib50% (n = 30)
     Nilotinib50% (n = 30)
    • * BCR-ABL1 kinase domain mutations: A387P (n = 1), M244V (n = 2), and H396R + F359V (n = 1).

  • Table 2.

    Potential prognostic factors for molecular relapse: univariate analysis

    VariableCumulative incidence of relapse by 48 mo (95% CI)Overall P value
    Age0.154
     >60 y (n = 28)54.78% (38.85-77.24)
      ≤60 y (n = 32)36.72% (22.49-59.95)
    Sex0.577
     Male (n = 22)36.36% (20.92-63.2)
     Female (n = 38)49.66% (35.45-69.55)
    Sokal score0.623
     Low (n = 32)42.71% (27.88-65.3)
     Intermediate + high (n = 25)49.1% (33.07-74.74)
    Prior IFN-α0.637
     Yes (n = 17)41.76% (23.67-73.7)
     No (n = 43)45.94% (32.65-64.64)
    TKI treatment duration0.643
     >76 mo (n = 30)47.11% (32.13-69.08)
      ≤76 mo (n = 30)42.29% (27.10-66)
    2G-TKI treatment duration0.772
     >39 mo (n = 29)44.83% (29.94-67.13)
      ≤39 mo (n = 31)44.31% (29.22-67.19)
    uMR4.5 duration0.597
     >29 mo (n = 29)37.93% (23.81-60.42)
      ≤29 mo (n = 31)50.52% (35.13-72.66)
    2G-TKI type0.331
     Dasatinib (n = 30)50.83% (35.52-72.76)
     Nilotinib (n = 30)38.62% (29.99-62.15)
    Prior intolerance or resistance to TKI0.00233
     Yes (n = 13)35.51% (23.73-53.15)
     No (n = 47)76.92% (57.11-100)
    • Quantitative variables were categorized into 2 groups with cutoffs set at median. P < .05 was considered statistically significant.