Safety Profile of Infectious Events for First-Line Pola-R-CHP Therapy in Elderly Patients with Diffuse Large B-Cell Lymphoma Including Those 80+ Years Old in Japan

Background and objectives

Safety data in elderly patients (pts) aged 80+ with diffuse large B-cell lymphoma (DLBCL) treated with Pola-R-CHP are limited. This study aims to describe the incidence of infectious adverse events and related events in elderly pts with DLBCL treated with Pola-R-CHP as their first line of therapy and in pts treated with R-CHOP as a control group.

Methods

A cohort study was conducted using a Japanese hospital-based administrative database from Medical Data Vision (UMIN000053834). Pts with DLBCL who were treated with Pola-R-CHP/R-CHOP between August 2022 and March 2023 were included at initiation of therapy. They were followed up during their first-line therapies until censoring or December 2023, including the 6th cycle at the latest. Descriptive analyses were performed to evaluate overall and cycle-specific incidences of febrile neutropenia (FN), intravenous (IV) antibiotic injection (antibacterial, antifungal, antiviral, sulfamethoxazole and trimethoprim [ST]), G-CSF usage, and transfusions. FN was defined by both blood culture testing and pre-specified antibacterial injection on the same day. Doses were calculated using the number of vials prescribed, weight, and/or height.

Results

The study included 618 pts in the Pola-R-CHP group and 1,332 pts in the R-CHOP group, with a median follow-up of or over 180 days. By age categories at cohort entry (<61, 61-69, 70-79, and 80+ years), 100 (16.2%), 151 (24.4%), 249 (40.3%), and 118 (19.1%) pts were in the Pola-R-CHP group whereas 197 (14.8%), 269 (20.2%), 493 (37.0%), and 373 (28.0%) were in the R-CHOP group, respectively. The proportion of pts receiving therapy for 6 cycles decreased over the age categories, from 84.0% at 61 < years to 63.6% at 80+ years in the Pola-R-CHP group and from 62.4% to 55.2% in the R-CHOP group.

The incidence proportions of FN were 14.0% (95%CI, 7.9- 22.4), 19.2% (13.3-26.4), 29.7% (24.1-35.8), and 23.7% (16.4-32.4) in the Pola-R-CHP group in the age categories of <61, 61-69, 70-79, and 80+ years while in the R-CHOP group, 9.1% (95%CI, 5.5-14.1), 20.4% (15.8-25.8), 29.0% (25.0-33.2), and 20.6% (16.6-25.1), respectively. The proportions of pts who used an IV antibacterial had a similar trend to that of FN among the age categories: 25.0% (16.9-34.7), 35.1% (27.5-43.3), 45.4% (39.1-51.8), and 39.8% (30.9-49.3) in the Pola-R-CHP group, and 25.4% (19.5-32.1), 37.5% (31.7-43.6), 43.2% (38.8-47.7), and 37.8% (32.9-42.9) in the R-CHOP group, respectively. FN and IV antibacterial use were observed most in the 1st cycles, 15.2% and 26.5% in the Pola-R-CHP group whereas in the R-CHOP group, 15.4% and 28.1%, respectively. Antifungal, antiviral, and ST injection were observed less frequently, with overall estimates of 4.2%, 7.4%, and 0.5% in the Pola-R-CHP group, and 3.8%, 5.0%, and 0.3% in the R-CHOP group, respectively.

Prophylactic G-CSF use before FN occurrence was 61.2% (57.2-65.0) in the Pola-R-CHP group and 51.5% (48.8-54.2) in the R-CHOP group for polyethylene glycol (PEG) G-CSF, 61.5% (57.5-65.3) and 61.5% (58.8-64.1) for daily G-CSF, respectively, with the lowest estimates in the age 80+ category, 46.6% and 47.7%, and 54.2% and 59.2%, respectively.

Cyclophosphamide (CPA) and Doxorubicin (DXR) were reduced in the 70-79 and 80+ age groups. The proportion of pts who received dose of 90% or more of standard dose of CPA in 1st cycle among pts aged 70-79 was 68.2% in the Pola-R-CHP group and 58.8% in the R-CHOP group, and that of DXR was 59.2% and 47.7%. Among pts aged 80+, these proportions were 22.9% and 19.7%, and 6.8% and 2.7%, respectively. In contrast, the proportion of Rituximab was 92.7% in the Pola-R-CHP and 84.7% in the R-CHOP group in those aged 70-79, and 88.1% and 80.0% in those aged 80+. That of Pola was 88.6% in those aged 70-79 and 75.4% in those aged 80+.

The respective proportions of pts receiving red blood cells in each of the >61 to 80+ year old age groups were 8.0%, 13.9%, 19.3%, and 23.7% in the Pola-R-CHP group and 8.6%, 14.5%, 22.1%, and 21.4% in the R-CHOP group. Those for pts receiving platelets were 3.0%, 7.3%, 8.8%, and 10.2% in the Pola-R-CHP group and 3.6%, 6.7%, 12.0%, and 7.8% in the R-CHOP group.

Conclusion

In both the Pola-R-CHP and R-CHOP therapy groups, the estimated incidences of FN and IV drug administration for infections in the age 80+ group were comparable to those in the age 70-79 group, with more dose reduction in the age 80+ group. Pola-R-CHP therapy may be as tolerable as R-CHOP therapy in pts aged 80+.