Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER Study
Menée sur 40 patients atteints d'une leucémie myéloïde chronique en phase chronique sans maladie résiduelle minimale détectable pendant au moins deux ans, cette étude évalue la faisabilité et l'efficacité d'une interruption de l'imatinib accompagnée de la recherche régulière d'une récidive moléculaire
Most patients with chronic myeloid leukemia (CML) treated with imatinib will relapse if treatment is withdrawn. We conducted a prospective clinical trial of imatinib withdrawal in 40 chronic phase CML patients who had sustained undetectable minimal residual disease (UMRD) by conventional Q-PCR on imatinib for at least 2 years. Patients stopped imatinib and were monitored frequently for molecular relapse. At 24 months the actuarial estimate of stable treatment-free remission was 47.1%. Most relapses occurred within 4 months of stopping imatinib, and no relapses beyond 27 months were seen. In the 21 patients treated with interferon before imatinib a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk, as was slower achievement of UMRD after switching to imatinib. Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD, even several years after imatinib withdrawal. No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations (median follow-up 42 months). All patients who relapsed remained sensitive to imatinib re-treatment. These 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. (Trial registered: ACTRN 12606000118505, http://www.anzctr.org.au/)