Updating Long-Term Outcome of Intermittent Imatinib (INTERIM) Treatment in Elderly Patients with Ph+-CML

BACKGROUND : The INTERIM study (ClinicalTrials.gov NCT 00858806) showed that in elderly (> 65 years) Ph+ CML patients selected for a stable complete cytogenetic response (CCgR) lasting > 2 years, the policy of intermittent imatinib treatment (one month on/one month off) may affect the markers of residual disease (CCgR and major molecular response, MMR or MR 3.0 ), but not the clinical outcomes (overall survival and progression-free survival) (Russo D et al, Blood 2013; 121(26):5138-44) . AIMS : To update the results of the INTERIM Study, with a follow up ≥ 5 years. METHODS : After 4 years of follow up, patients continouing INTERIM treatment were monitored with peripheral blood RT-Q-PCR every 3 months according to the ELN-2013 guidelines. RESULTS : At 48 th month, out of 76 patients enrolled in the INTERIM study, 13 (17%) had lost CCgR and MMR, 14 (18%) had lost MMR only and 50 patients (75%) continued INTERIM. The patients who had lost CCgR and/or MMR resumed imatinib continuously and all of them regained the CCgR and the MMR, within 3 to 12 months. No patient progressed to accelerated or blastic phase, or developed clonal chromosomal abnormalities in Ph+ cells, or BCR-ABL mutations. No patient complained of new or more severe side effects during the months “on”. After a follow up ≥ 5 years, 45/76 (59%) enrolled patients are on INTERIM, with a probability of maintaining intermittent administration of 59% (95% CI: 46-69). No patient lost the CCgR and only 9 additional patients lost the MMR while on intermittent treatment. All these patients resumed continuous imatinib treatment and regained the MMR. Thus, at ≥ 5 years, the probability of maintaing CCgR is 80% (95% CI 68-87) and the probability of maintaining the MMR is 61% (95% CI: 48-71). From start of INTERIM, 6 patients died but no deaths were related to CML progression (3 cases of other non haematological neoplasms, 1 stroke, 1 myocardial infarction, 1 chronic obstructive pulmonary disease).The PFS at ≥ 5 years is 94% (95% CI: 89-100) CONCLUSIONS: In summary, with a follow up ≥ 5 years, intermittent imatinib administration (INTERIM) confirmed to be safe, to produce a reversible increase of residual molecular disease in about one third of patients, but not to affect the long-term outcome. Aknowledgments: This work was supported in part by EuropeanLeukemiaNet (contract LSHC-CT-2004-503216) through the European Treatment and Outcome Study (EUTOS), supported by Novartis Oncology Europe, and COFIN 2009 Disclosures Russo: Celgene: Research Funding; Gilead: Research Funding; Novartis: Consultancy. Martinelli: Novartis: Speakers Bureau; Bristol-Meyers and Squibb: Speakers Bureau; Pfizer: Speakers Bureau. Soverini: Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria; Ariad: Consultancy, Speakers Bureau. Turri: Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Castagnetti: Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Breccia: novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Abruzzese: Novartis: Consultancy. Tiribelli: Novartis: Consultancy, Honoraria; Bristol-Meyers and Squibb: Consultancy, Honoraria. Rosti: Consultant: Consultancy, Speakers Bureau; Bristol-Meiers Squibb: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.