80% Dose R-CHOP Is Suitable Chemotherapy for Very Elderly Patients with DLBCL
Authors: Takahashi Anna , Mishima Yuko , Inoue Norihito , Kusano Yoshiharu , Gunji Tadahiro , Ueda Kyoko , Nishimura Noriko , Nitta Hideaki , Yokoyama Masahiro , Tsuyama Naoko , Takeuchi Kengo , Terui Yasuhito , Hatake Kiyohiko 
Published: October 2019

Abstract
Introduction: R-CHOP therapy is standard chemotherapy for DLBCL. In the LNH98-5 study, CR was 75% and 5-year EFS was 63% in low-risk patients and 41% in high-risk patients. Five-year OS was 80% in the low-risk group, and 48% in the high-risk group. R-CHOP is tolerable and commonly applied to outpatients. However, almost 20% of patients with DLBCL were very elderly, 75 years of age or more. Chemotherapy for very-elderly patients often causes many troubles, and thus the prognosis is worse than those of younger patients. The dose of R-CHOP therapy for the elderly patients varies among institutions because there are no suitable guidelines for it. Therefore, the optimal dose of R-CHOP therapy is needed to be determined to improve the outcome of the elderly patients with DLBCL.
Methods: We reviewed the clinical records of 91 newly-diagnosed very-elderly (≥75 years) patients with DLBCL. All of the patients were diagnosed by hematopathologists, and treated with R-CHOP-based chemotherapy in our hospital from 2005 to 2015. Clinical stage and the effect of therapy were evaluated with PET/CT scan. Statistical analyses were performed with a software, EZR version 1.
Results: The total number of patients with DLBCL in the study period was 373, including 91 very-elderly patients (24%). The characteristics of very elderly patients were following; the median age was 78 years (range 75-86), the median follow-up period was 1,068 days (range 39-2,989), 49 (54%) were male, 38 (43%) were at stage III or IV, 39 (43%) had IPI high or intermediate risk, bulky disease (≥10 cm) was observed in 18 (20%), and 75 (82%) showed ECOG PS 0 or 1. Twenty-six patients (29%) were treated with R-CHOP at full dose, 64 patients (70%) at 80%, and one was at 70%. In the 80% R-CHOP group, the dose was decreased to 70% in 5 patients, because of severe adverse events (febrile neutropenia in three, grade 3 nausea and grade 3 weakness, each in one). The median ages of patients were 76 years in the full dose group (range 75-79) and 78 years in the 80% dose group (range 75-86). In the all very-elderly patients, 5-year OS was 66% (95% CI, 52-77%) and 5-year PFS was 68% (95% CI, 55-78%). CR was achieved in 73% in the full-dose group, and 67% in the 80% dose group. Five-year OS were 77% in the full-dose group, and 61% in the 80% dose group (P=0.129). Five-year PFS were 82% in the full-dose group, and 63% in the 80% dose group (P=0.117). Five-year OS were 100% in the IPI low group, 65% in the low- and high-intermediate groups, 0% in the high group (P<0.001). Twenty-six patients died: 13 for progression of lymphoma, 7 for other diseases, and 6 for unknown causes. All patients with 5 IPI indexes died of lymphoma. Twenty-one patients completed the therapy (81%) in the full-dose R-CHOP group, and 55 (86%) in the 80% R-CHOP group. In the 14 patients who could not complete the therapy, 7 achieved CR without relapse. The most frequent adverse event was hematological toxicity. Neutropenia at grade 3 or 4 was observed in 17 (19%), and febrile neutropenia in 12 (13%). No treatment-related deaths were observed.
Conclusions: In the very elderly patients, there were no significant differences in 5-year OS and PFS between the full-dose R-CHOP and the 80% R-CHOP groups. Prognosis was very poor for the patients with IPI high risk, especially with 5 IPI indexes. Our data suggested that 80% dose R-CHOP is enough tolerable and effective to very elderly patients with DLBCL categorized in IPI high-intermediate or lower risks.

Disclosures
Mishima: Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.