Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of extranodal large B-cell lymphoma characterized by selective growth of lymphoma cells in the lumina of small vessels. The prognosis of IVLBCL is typically poor without timely diagnosis. Based on the promising efficacy of rituximab-containing chemotherapy and a high incidence of secondary central nervous system (CNS) involvement after rituximab-chemotherapy, we conducted the PRIMEUR-IVL study to explore the efficacy of CNS-oriented therapy with rituximab-chemotherapy whose primary analysis demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence of secondary CNS involvement of 3%. Patients and Methods: The PRIMEUR-IVL study is a multicenter, single-arm, phase 2 trial at 22 hospitals in Japan for untreated histologically confirmed IVLBCL patients without apparent CNS involvement at diagnosis. The treatment regimen includes three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by two cycles of rituximab with high-dose methotrexate and additional three cycles of R-CHOP. Intrathecal chemotherapy including methotrexate, cytarabine, and prednisolone was administered four times during the R-CHOP phase. We present a preplanned final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and secondary CNS involvement. Results: A total of 38 patients were enrolled, of whom 37 patients were eligible. One patient with a history of testicular lymphoma was excluded. As of July 2021, with a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). Median PFS and OS were not reached. No additional secondary CNS involvement was observed after primary analysis with 3% of cumulative incidence. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). During the observation period after enrollment, there were a total of eight deaths due to following reasons: primary disease (n = 6), sepsis (n = 1), and unknown sudden death (n = 1). Conclusions: In this 5-year, long-term follow-up analysis of the PRIMEUR-IVL study, frontline treatment of CNS-oriented therapy with standard R-CHOP for untreated IVLBCL patients without apparent CNS involvement provided durable response and clinically meaningful results for PFS, OS, and low incidence of secondary CNS involvement with manageable toxicity. Our result provides one of active treatment for untreated IVLBCL patients. The research was funded by: The Practical Research for Innovative Cancer Control, the Japan Agency for Medical Research and Development (AMED), Japan, JP19ck0106511 and the National Cancer Center Research and Development Fund, 23-A-17 and 26-A-4. The research was supported by the Center for Supporting Hematology-Oncology Trials (C-SHOT). Keyword: chemotherapy Conflicts of interests pertinent to the abstract K. Shimada Honoraria: AstraZeneca, Chugai, Eisai, Kyowa Kirin, Symbio M. Yamaguchi Honoraria: AbbVie, Bristol Myers Squibb, Chugai, Janssen, Kyowa Kirin, Meiji Seika, MSD, Nippon Shinyaku, SymBio, Takeda Research funding: AstraZeneca, Chugai Pharma, Genmab, Incyte, Eisai, Takeda, Nippon Shinyaku, Otsuka, Asahi Kasei, Kyowa Kirin, Chugai H. Nagai Honoraria: Kyowa Kirin, Takeda, Chugai, Bristol Myers Squibb, Eisai, Novartis, Janssen, Mundi Pharma, Lilly, AstraZeneca, Ono, Meiji, AbbVie, Nippon Shinyaku, GSK, Sumitomo Pharma, Genmab, CSL Behring Research funding: Kyowa Kirin, Takeda, Chugai, Bristol Myers Squibb, Janssen, AstraZeneca, Ono, AbbVie, Nippon Shinyaku, Daiichi-Sankyo, Zenyaku Kogyo, Solasia J. Takizawa Honoraria: Chugai, Kyowa Kirin N. Fukuhara Honoraria: Chugai, Genmab, AbbVie, Takeda, Eli Lilly, AstraZeneca, Meiji Seika, Ono, Janssen, Bristol-Myers Squibb, Eisai, Kyowa Kirin, Symbio, Novartis Research funding: Chugai, Genmab, AbbVie, Takeda, Eli Lilly, Incyte, Chordia Therapeu D. Ennishi Honoraria: Eisai, Kyowa Kirin, Chugai Research funding: Nippon Shinyaku, Chugai Y. Minami Consultant or advisory role: Takeda, Novartis Honoraria: Bristol-Myers Squibb, Novartis, Pfizer, Daiichi Sankyo, Astellas Research funding: CMIC, Bristol-Myers Squibb, Novartis, Takeda, Chugai, Ono Y. Atsuta Consultant or advisory role: Meiji Seika, JCR Pharmaceuticals, Kyowa Kirin Honoraria: Novartis, AbbVie H. Kiyoi Honoraria: Novartis, Astellas, AbbVie, Chugai Research funding: Zenyaku Kogyo, Nippon Shinyaku, Chugai, Astellas, Kyowa Kirin, Takeda, Sumitomo Pharma, Sanofi, Eisai, Ono, FUJIFILM, Kyowa Kirin, Otsuka, Perseus Proteomics, Daiichi Sankyo, CURED, Bristol-Myers Squibb, AbbVie
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Oct 1, 2023
Toshio Morikawa 
Open Access
