Weekly Four Times Rituximab Consolidation Following Reduced Cycles Of R-CHOP Induction Chemotherapy In Extremely Elderly Patients With Diffuse Large B Cell Lymphoma
Authors: Yang Deok-Hwan , Kim Won Seog , Do Young-Rok , Oh Sung Yong , Kim Min Kyoung , Mun Yeung-Chul , Shin Ho-Jin , Kwak Jae-Yong , Kang Hye Jin , Won Jong-Ho , Kwon Jung hye , Kim Hyo Jung , Suh Cheolwon , Lee Je-Jung 
Published: October 2019

Abstract

Purpose
Poor outcome of patients with elderly diffuse large B-cell lymphoma (DLBCL) has been linked to their decreased ability to receive full course of R-CHOP, dose-reduction of chemotherapy due to toxicities and their concomitant disease to interrupt the treatment. Recently, several studies suggested that attenuated R-CHOP regimen or reduced cycles of R-CHOP showed the survival benefit along with good tolerability and safety for very elderly patients. The study is aimed to determine objective response, toxicitiy and clinical outcome of weekly four times rituximab augmentation after reduced cycles of R-CHOP in extremely elderly patients with DLBCL.

Patients and Methods
Prospective, multi-institutional phase II trial was conducted for patients with previously untreated CD20+ diffuse large B cell lymphoma who aged more than 70 years and achieved complete or partial response after 4th R-CHOP chemotherapy (NCT01181999). R-CHOP was infused every 21 days, with initial dose-intensity of CHOP regimen was modulated according to Charlson Comorbidity Index (CCI). If patients were with CCI <1, patients were treated with standard dose of CHOP, however, if patients with CCI °Ã1, patients were with 75% of conventional dose initially. Rituximab consolidation (375mg/m2) was treated weekly four times, at the time of full recovery after 4th R-CHOP. Trimethoprim/sulfamethoxasole (160mg/800mg, 1T orally) was given daily during rituximab consolidation. Response assessment based on Revised International Workshop Criteria was evaluated at the completion of the fourth R-CHOP, after rituximab consolidation and whenever disease progression is suspected.

Results
51 DLBCL patients were enrolled from 14 institutes between June 2010 and April 2013. Median age was 76 years (range: 70-89) and 35.3% patients had more than 2 concomitant chronic disease. 36 out of 51 patients could be proceeded toward weekly four times rituximab consolidation. High treatment-related mortality (13.7%) during R-CHOP was huddle to proceeding to consolidation treatment. 35 patients (68.6%) presented with high-intermediate or high risk based on IPI and 12 patients (23.5%) were classified with a score of 2 by Glasgow prognostic score (GPS). After a median follow-up of 18.6 months, overall response rate was 70.6% with 66.7% of complete response and 3.9% of partial response. 31 patients (60.8%) were started with decreased dose of CHOP with median 75% reduction of CHOP (range; 50-100%). 2-year probability of progression-free survival (PFS) was 71.5 ±7.9% with 10 relapses. GPS based on systemic inflammatory indicators was a useful prognostic indicator for PFS compared to IPI. The adverse events were mainly related with hematologic toxicities and neutropenic infections during R-CHOP. However, no toxicities were reported associated with rituximab weekly infusion and no adverse events related with delayed infection after rituximab consolidation.

Conclusions
Rituximab consolidation after reduced cycles of R-CHOP resulted in a favorable response with high tolerability. Debulking R-CHOP and followed by weekly rituximab consolidation could be a good compromise between efficacy and tolerability for extremely elderly DLBCL

Disclosures:
No relevant conflicts of interest to declare.