Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia.

@article{tienne2017LongTermFO,
  title={Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia.},
  author={Gabriel {\'E}tienne and Joelle Guilhot and Delphine R{\'e}a and Françoise Rigal‐Huguet and Franck Emmanuel Nicolini and Aude Charbonnier and Agn{\'e}s Guerci-Bresler and Laurence Legros and B. Varet and Martine Gardembas and Viviane Dubruille and Micheline Tulliez and Marie Pierre Noel and Jean-Christophe Ianotto and Bruno Villemagne and Martin Carr{\'e} and François Guilhot and Philippe Rousselot and François Xavier Mahon},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  year={2017},
  volume={35 3},
  pages={
          298-305
        }
}
  • G. ÉtienneJ. Guilhot F. Mahon
  • Published 20 January 2017
  • Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. [] Key Method Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years.

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References

SHOWING 1-10 OF 44 REFERENCES

Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years.

It is hypothesized that relapses observed within 6 months reflect the kinetics of undetectable dividing chronic myelogenous leukemia (CML) cells, which may be eradicated or controlled in long-term nonrelapsing patients, as described in the study.

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

In conclusion, discontinuation of first-line or subsequent 2G-TKI yields promising TFR rates without safety concerns and a landmark analysis demonstrated that loss of MR4.5 3 months after stopping TKI was predictive of failure to maintain MMR later on.

Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease.

Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR, and should be a criterion for resuming therapy.

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib

The data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post‐transplant relapse.

Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia

During the sixth year of study treatment, there were no reports of disease progression to accelerated phase (AP) or blast crisis (BC), and the toxicity profile was unchanged.

Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study.

The results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse, and show persistence of the original CML clone in all patients with stable U MRD, even several years after imatinIB withdrawal.

Preliminary Report Of The STIM2 Study: A Multicenter Stop Imatinib Trial For Chronic Phase Chronic Myeloid Leukemia De Novo Patients On Imatinib

It is confirmed that Imatinib can be safely and prospectively discontinued in pts with DMR of at least 2 years duration in patients only treated with imatinib and that all patients were sensitive to a TKI re-challenge.

Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study

Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before Imatinib discontinuation were associated with a higher probability of sustained major molecular response and minimal residual leukemia measured by digital polymerases chain reaction had a trend for a higher molecular relapse.

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial

Long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP, and few deaths in any arm were associated with CVEs, infections or pulmonary diseases.