Updating Long-Term Outcome of Intermittent Imatinib (INTERIM) Treatment in Elderly Patients with Ph+-CML
Authors: Russo Domenico , Martinelli Giovanni , Malagola Michele , Cancelli Valeria , Skert Cristina , Soverini Simona , Iacobucci Ilaria , Turri Diamante , Mirto Salvatore , Gobbi Marco , Pierri Ivana , Vitolo Umberto , Pregno Patrizia , Fogli Miriam , Testoni Nicoletta , De Vivo Antonio , Castagnetti Fausto , Morra Enrica , Pungolino Ester , Di Raimondo Francesco , Stagno Fabio , Alimena Giuliana , Breccia Massimo , Nobile Francesco , Martino Bruno , Rambaldi Alessandro , Intermesoli Tamara , Saglio Giuseppe , Rege Cambrin Giovanna , Visani Giuseppe , Nicolini Giuseppina , de Fabritiis Paolo , Abruzzese Elisabetta , Fanin Renato , Tiribelli Mario , Galieni Piero , Bigazzi Catia , Specchia Giorgina , Angelucci Emanuele , Usala Emilio , Musolino Caterina , Russo Sabina , Gaidano Gianluca , Lunghi Monia , Lauria Francesco , Bocchia Monica , Rodeghiero Francesco , D'Emilio Anna , Bosi Alberto , Santini Valeria , Quarta Giovanni , Girasoli Mariella , Fioritoni Giuseppe , Di Lorenzo Roberto , Cesana Bruno Mario , Rosti Gianantonio 
Published: October 2019

Abstract

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 MR3.0), 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 48thmonth, 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.