A Multicenter, Prospective, Observational Study of Pola-R-CHP in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (POLASTAR): A Preliminary Analysis

Background: Based on the results of the POLARIX study (NCT03274492; Tilly et al. N Engl J Med 2022), polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) was approved in 2022 for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) in Japan. Currently, there are no comprehensive reports on the real-world usage of this regimen in Japan. This analysis of the real-world POLASTAR study (jRCT1071220082) provides information on the patient characteristics and safety data of Japanese patients with previously untreated DLBCL treated with Pola-R-CHP in a clinical setting.

Methods: POLASTAR is a multicenter, prospective observational study in Japan. The target sample size of this study was 500 patients; patients were included if they were ≥18 years, had previously untreated DLBCL, and received Pola-R-CHP per the latest Package Insert as part of their routine care (initial dose reduction was permitted). Patients excluded from POLARIX, such as those aged >80 years, were included in this study based on the physicians' decision. The primary endpoint of POLASTAR was overall survival. This preliminary analysis aimed to evaluate the safety and response rate at end of treatment (EOT) of the first 200 patients prospectively enrolled in the POLASTAR study. Here we report Grade ≥3 adverse events (AEs) and AEs leading to polatuzumab vedotin discontinuation, complete response rate (CRR) at EOT, and overall response rate (ORR) at EOT.

Results: Between 9 February 2023 and 6 December 2023, a total of 502 patients were prospectively enrolled across 71 sites. At data cut-off (20 December 2023),of the initial 200 patients enrolled, 192 (96.0%) were identified and included in the full analysis set. Median age was 71 years (range 30-91); age >80 years, n=25/192 (13.0%); Eastern Cooperative Oncology Group Performance Status 0-2, n=179/188 (95.2%); International Prognostic Index 2-5, n=134/188 (71.3%); Ann Arbor Stage III-IV, n=116/192 (60.4%); and bulky disease (≥7.5 cm), n=28/192 (14.6%). Median time from initial diagnosis to treatment initiation was 26.5 days (range 4.0-327.0). At data cut-off, the majority of patients (n=163/185; 88.1%) had completed planned treatment with Pola-R-CHP; seven patients were still ongoing treatment.

In total, 99 (51.6%) patients had Grade ≥3 AEs, and 29 (15.1%) had serious AEs. Most common Grade ≥3 AEs included neutrophil count decreased (n=54; 28.1%), white blood cell decreased (n=22; 11.5%), and febrile neutropenia (n=19; 9.9%). Among patients >80 years (n=25), the most common Grade ≥3 AEs included neutrophil count decreased (n=7; 28.0%) and febrile neutropenia (n=6; 24.0%). Grade ≥3 febrile neutropenia was numerically higher in patients >80 years compared with the overall population (24.0% [n=6] vs 9.9% [n=19]). A total of two deaths were reported (sepsis, n=1; pneumonitis, n=1). Fifteen (7.8%) patients discontinued polatuzumab vedotin due to AEs, and the most common AEs leading to treatment discontinuation included peripheral sensory neuropathy (n=3), lung infection (n=2), and COVID-19 infection (n=2). No new safety signals were observed. In the efficacy-evaluable population at EOT (n=141), ORR was 95.0% (95% confidence interval [CI]: 90.1-97.6), and CRR was 87.9% (95% CI: 81.5-92.3).

Conclusions: At the time of this preliminary analysis of the initial 200 patients enrolled, efficacy and safety of Pola-R-CHP in Japanese patients were consistent with previously published results from POLARIX. The POLASTAR study is ongoing and the planned enrollment of 500 patients has completed. Patients are currently under observation and further evaluation of the study will be reported both at future congresses and in future publications.

Shibayama:Bristol Myers Squibb, AbbVie, Novartis: Research Funding; AstraZeneca, Ono, Chugai, Nippon-Shinyaku, Janssen, Fujimoto, Meiji Seika Pharma, Sanofi, AbbVie, Takeda, Bristol Myers Squibb, Novartis, Amgen: Speakers Bureau; Chugai, AbbVie: Membership on an entity's Board of Directors or advisory committees. Satake:Chugai: Honoraria. Ota:Novartis, Bristol Myers Squibb, Takeda Pharmaceutical Company Limited, AstraZeneca, Janssen, AbbVie, Amgen, Sanofi, PharmaEssentia: Honoraria. Muta:Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital: Current Employment. Suzuki:Chugai, Kyowa-Kirin, AbbVie, Bristol-Meyers Squibb, Eisai, Ohtsuka, MSD, Janssen, Takeda, Meiji-Seika, Novartis, AstraZeneca: Honoraria; Chugai, Kyowa-Kirin, Shionogi, Taiho, Eisai, Ohtsuka: Research Funding. Miyake:Janssen, Sanofi, Chugai, AstraZeneca, Bristol Myers Squibb, Meiji Seika Pharma, Ono: Honoraria. Goto:Novartis, BMS, Gilead, Chugai, Kyowa-Kirin, AbbVie, MSD: Honoraria; Sanofi, BMS, Kyowa-Kirin: Research Funding. Fukuhara:Chugai Pharma: Honoraria, Research Funding; Eisai: Honoraria; Takeda: Honoraria, Research Funding; Gilead: Honoraria; Bristol Myers Squibb: Honoraria; LOXO Oncology: Research Funding; Chordia Therapeutics: Research Funding; Genmab: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Janssen: Honoraria; Nippon kayaku: Honoraria; Eli Lilly: Honoraria; Meiji Seika: Honoraria; Incyte and Takeda: Research Funding; AbbVie: Honoraria, Research Funding; AstraZeneca: Honoraria; Soreisia: Honoraria; Ono: Honoraria; Novartis: Honoraria. Sakata-Yanagimoto:Chugai Pharma, Eisai, Bristol Myers Squibb: Research Funding; LSI Medience: Patents & Royalties; Chugai Pharma, Eisai, Meiji Seika, Janssen, AbbVie, Astellas, Kyowa Kirin, Takeda, Nippon Kayaku, MSD, Nippon Shinyaku: Speakers Bureau. Izutsu:Ono Pharma, Symbio, Takeda: Consultancy, Honoraria; Beigene, Yakult, Otsuka: Consultancy, Research Funding; Pfizer, Janssen, Gilead, Daiichi Sankyo: Honoraria, Research Funding; Incyte, Bayer, O Oncology, Regeneron: Research Funding; MSD, AstraZeneca, Genmab, Chugai, BMS, Kyowa Kirin, Novartis, AbbVie: Consultancy, Honoraria, Research Funding; AstraZeneca, Eli Lily, Astellas, Ono Pharmaceuticals, Eisai, Chugai, Janssen, Symbio, Bristol Myers Squibb, Daiichi Sankyo, Otsuka, Abbvie, Takeda, Eli Lilly, Genmab, Kyowa Kirin, MSD, Astellas, Pfizer, MeijiSeika Pharma, Novartis, Nihon Kayaku, Gilead,: Honoraria; MSD, AstraZeneca, Abbvie, Incyte, Bristol Myers Squibb, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, Daiichi Sankyo, Chugai, Beigene, Genmab, LOXO Oncology, Otsuka, Regeneron, Gilead: Research Funding; AstraZeneca, Zenyaku, Ono Pharmaceuticals, Mitsubishi Tanabe Pharma, Eisai, Chugai, Bristol Myers Squibb, Takeda, Otsuka, Abbvie, Zenyaku, Kyowa Kirin, MSD, Carna Biosciences, Novartis, Yakult, Nihon Shinyaku, Abe Pharma, Eisai,Beigene: Consultancy. Nishikori:SymBio Pharmaceuticals: Research Funding; Sumitomo Pharma, AstraZeneca, AbbVie, Otsuka, Chugai, Ono Pharmaceutical, Kyowa Kirin, SymBio, Genmab, Takeda, Nippon Shinyaku, Bristol Myers Squibb, Janssen Pharma, Ohara Pharmaceutical: Honoraria. Kumode:Janssen Pharmaceutical, Ono Pharmaceutical: Speakers Bureau. Ennishi:Nipponshinyaku Pharmaceutical Co., Ltd.: Honoraria, Research Funding; AbbVie: Honoraria; Astrazeneca: Honoraria; Bristol-Myers Squibb: Honoraria; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; SymBio Pharmaceuticals: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; Novartis: Honoraria; Kyowa-Kirin: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Illumina, Inc: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Eisai Pharmaceutical Co., Ltd.: Honoraria, Research Funding. Inubashiri:Chugai Pharmaceutical Co., Ltd.: Current Employment; Asahi Co., Ltd.: Divested equity in a private or publicly-traded company in the past 24 months. Matsumura:Otsuka Pharmaceutical: Consultancy, Honoraria, Research Funding; TAIHO PHARMACEUTICAL CO., LTD.: Research Funding; Sumitomo Pharma: Research Funding; Bristol-Myers Squibb Company: Honoraria, Research Funding; AbbVie GK.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Kyowa Kirin Co., Ltd.: Research Funding; ASAHI KASEI PHARMA CORPORATION: Honoraria; Astellas Pharma: Honoraria; AstraZeneca: Honoraria; Eisai Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K: Honoraria; Novartis Pharma KK: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria.