Background. CHOP, recently combined to the first in class anti CD20immunotherapy, is the leading regimen worldwide for the treatment of high grade B cell non Hodgkin lymphoma (DLBCL). Over the years, improvement have been made to CHOP in order to enhance its efficacy, although no development were made to improve its convenience, indeed, most of the CHOP chemotherapy are IV based. We sought to demonstrate that oral topoisomerase inhibitors III (idarubicin, I) in combination with oral cyclophosphamide (C), etoposide (E, celltop), and prednisolone (P) would prove similar efficacy with an improved convenience to patients.

Patients and Methods: This phase 1/2 study was performed to determine the maximum-tolerated dose (MTD) of oral idarubicin in combination with oral C, E, P keeping IV rituximab (R). The patients were to be previously untreated DLBCL stage III or IV, aged 60 to 80 years old. Secondary objectives included evaluation of toxicity and efficacy. The MTD was defined as the dose level at which at least 2 of 3, and if none then 3 of 6 patients experienced a DLT. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia lasting at least 4 days or grade 4 thrombopenia or more than grade 2 extra hematological toxicity.

I was administrated on day 1 at 20, 30, 40mg/m2. No intrapatient dose escalatation was allowed. C and E were given on day 1 to 3 at the fixed dose of 150 mg/m2 and 100 mg/m2 respectively. P was given at the fixed dose of 50 mg/m2 on day 1 to 5. R was administrated IV on day 1 at the fixed dose of 375 mg/m2. G-CSF was systematically used from day 6 to hematological reconstitution. Eight cycles were planned at 3 week-intervals.

Results: Twenty six pts were recruited, median age 71 (range 62-80). Overall, 180 cycles at 3 different I dose levels were administered. Although no DLT was observed at dose level 1 (20 mg/m2), 2 of 6 patients developed a DLT at dose level 2 (30 mg/m2), and eventually, all first 3 patients developed a DLT at level 3 (40 mg/m2) which was then considered as MTD. Fourteen patients were then enrolled for the phase 2 portion at the RP2D of 30mg/m². Main toxicity results are summarized in the table below. No toxic related mortality was observed. Two patients stopped treatment because of toxicity and 10 patients received a decreased dose of ID. Overall response rate and complete response rate were 80% and 73%, respectively. With a median follow-up of 4.5 years (9.5 years for alive patients), the 5-year overall survival and event free survival were 65% (95%CI: 41;81) and 65% (95%CI: 42;81), respectively.

Conclusion. This study shows that all oral OroCIEP regimen for elderly disseminated DLBCL demonstrated similar efficacy (Coiffier et al, NEJM 2002) with improved convenience to patients, especially elderly as studied in our trial. Subcutaneous anti-CD20 antibody treatment will represent a future improvement towards an all 'at home' regimen. This data needs validation in a larger cohort.

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Disclosures

Leleu: Janssen: 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; Takeda: 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; Celgene: 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; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: 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.

Topics:
cyclophosphamide, etoposide, idarubicin, lymphoma, non-hodgkin, older adult, prednisolone, rituximab, toxic effect, cyclophosphamide, doxorubicin, prednisone, and vincristine, diffuse large b-cell lymphoma

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2017 by The American Society of Hematology
2017
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