Abstract
Background. The Doxorubicin based R-CHOP regimen remains the standard of care for the upfront treatment of DLBCL. The advent of oral idarubicin permitted to develop an all-oral ambulatory oro-CIEP regimen. We hypothesized this regimen would improve the treatment of elderly DLBCL.
Methods. We have performed a phase 1/2 study to determine the MTD of idarubicin in the oro-CIEP regimen. Idarubicin was orally administrated on day 1 with starting dose at 20mg/m2 and escalated per 10mg/m2 increment.
Results. Twenty-six newly diagnosed patients were enrolled, median age of 71 years (range, 62-80). All first 3 patients developed a DLT at level 3 (40mg/m2), and 14 patients were then enrolled at RP2D 30mg/m² in the phase 2. The most significant hematological toxicities were thrombocytopenia grade 3 or 4 (3.3%) and neutropenia grade 3 or 4 (26%); and extra-hematological toxicities were infectious disease (5% grade 3 or 4). No toxic related death was observed. ORR and CR rates were 85% and 77%, respectively. The 5-year overall survival and event free survival were 65% (95%CI 41;81) and 65% (95%CI 42;81), respectively.
Conclusion. This analysis shows that oral idarubicin at the MTD of 30 mg/m2 is safe and active in elderly DLBCL. The results we have observed, particularly overall survival seemed to be superimposable to previous publications with the regular CHOP-like regimens for this population. Further improvements in the protocol will be introduced with the subcutaneous anti-CD20 immunotherapy approach. This data needs to be confirmed in the context of a larger study.
Leleu:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.
Author notes
Asterisk with author names denotes non-ASH members.
