Efficacy and Safety of R-Mini-CHP Administered in Combination with Polatuzumab Vedotin (Pola-R-mini-CHP) in Patients ≥80 Years Old with Diffuse Large B-Cell Lymphoma in the Real-World Setting: A Single-Institute Retrospective Study
Authors: Sekiguchi Yasunobu , Tsutsumi Hiroki , Kudou Masahisa , Maseki Nobuo , Iizaki Yoshie , Kobayashi Kazuhiko , Nishimura You , Takei Daisuke , Abe Tomoya , Kobayashi Hirofumi 
Published: December 2024

BACKGROUND
In the POLARIX study conducted in previously untreated patients(Pts) with diffuse large B-cell lymphoma (DLBCL), the Pola-R-CHP arm showed significantly improved progression-free survival (PFS) as compared with the R-CHOP arm. Therefore, Pola-R-CHP was approved in Japan, ahead of elsewhere in the world. However, the efficacy and safety of this treatment in Pts aged ≥80 years old remains unknown since there is little evidence in this age group. Therefore, we conducted this single-institute retrospective observational study to evaluate the efficacy and safety of the Pola-R-CHP regimen in this age group in clinical practice. A clinical study (Polar Bear) is currently under way.

METHODS
Treatment-naive DLBCL Pts aged ≥80 years old seen between September 2022 and May 2024 at the Saitama Cancer Center received Pola-R-mini-CHP at 3-week intervals. The Pola-R-mini-CHP regimen consisted of rituximab 375 mg/m2, cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, and polatuzumab vedotin 1.8 mg/kg administered on Day 1 of each treatment cycle, plus prednisolone 40 mg/m2 administered on Days 1 to 5. The primary endpoint was the overall response rate (ORR, complete remission [CR] plus partial remission [PR]) at the completion of treatment. The secondary endpoints were the PFS, overall survival (OS), severity and frequency of adverse events(AEs), and non-relapse mortality (NRM).

RESULTS
A total of 23 Pts were enrolled in the study. The median age was 83 (range 80-92) years, and 60.9% (14/23) were male. The Charlson Comorbidity Index (CCI) was 2 in 9/23 Pts (39.1%), and ≥3 in 14/23 Pts (60.9%). Of all the 23 Pts, 13 (56.5%) had a prior history of malignant disease. The performance status (PS) was ≥2 in 8/23 Pts (34.8%). The Ann Arbor stage was III to IV in 18/23 Pts (78.3%). The serum LDH level exceeded the institutional upper limit in 9/23 Pts (39.1%). The serum albumin level was &lt;4.1 mg/dL in 15/23 Pts (65.2%). The serumβ2MG level was ≥2.0 mg/dL in 20/23 Pts (87%). The number of extranodal sites was ≥2 in 8/23 Pts (34.8%); 2/23 Pts (8.7%) had a bulky mass. The International Prognostic Index (IPI) was ≥2 in 21/23 Pts (91.3%). Of the 23 Pts, 11 (47.8%) had the GCB type and 12 (52.2%) had the non-GCB type; 4 Pts (17.4%) had double-expressor lymphoma (DEL), and 1 Pt (4.3%) had double-hit lymphoma (DHL). The tumor cells showed CD5 positivity in 5/23 Pts (21.7%). Prophylactic Peg-G-CSF was administered to all the 23 Pts (100%). The median follow-up was 8.9 months, and the median number of treatment cycles was 8 (range, 2-8). The treatment was completed (8 cycles) in 15/23 Pts (65.2%).
All the Pts (n = 15) who underwent imaging evaluation at the end of treatment (EOT), or a pathological autopsy during treatment showed CR (CRR, 100%). There were no Pts who showed PR, stable disease (SD), progressive disease (PD), or relapse. One of the 23 Pts (4.3%) died due to acute exacerbation of interstitial pneumonia. The cumulative survival rate from the date of diagnosis was 94.7%.

The most common AE was hematological toxicity
grade 3/4 anemia, neutropenia, leukopenia, and thrombocytopenia were observed in 17.4%, 17.4%, 13.0%, and 4.3%, respectively. The incidence of anemia peaked immediately after the end of the 6th cycle of treatment, and decreased after the 7th cycle. There were no cases of febrile neutropenia (FN). Non-hematological toxicities of ≥grade 3 observed were grade 3 COVID-19 pneumonia (4.3%), grade 3 bacteremia (4.3%), and grade 5 interstitial pneumonia(IP) (4.3%). Mild constipation and mild peripheral neuropathy were noted in 21.7% and 4.3%, respectively. None of the Pts developed diarrhea. The treatment was discontinued in 2/23 Pts: at the patient's request in one patient and due to the development of chronic subdural hematoma as a result of head contusion in the other.

CONCLUSIONS
Pola-R-mini-CHP was concluded as being effective and safe in DLBCL patients aged ≥80 years old. Attention needs to be paid to the development of anemia especially up to the 6th cycle of treatment. We encountered one death due to IP, the causal relationship of which to Pola-R-mini-CHP could not be ruled out. In the future, we propose to compare the efficacy and safety of Pola-R-mini-CHP and R-mini-CHOP by propensity score matching analysis.