Type: Oral
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Novel Treatment Strategies and New Data on Old Standards for Follicular Lymphoma
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Lymphomas, Clinical Research, Diseases, Indolent lymphoma, Lymphoid Malignancies, Study Population, Human
Patients and Methods: In this study, LTB-FL by Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria were divided into two groups; very low tumor burden (the largest mass <5 cm, two or less nodal sites [each ≥3 cm], no effusion), and intermediate tumor burden (one or more of the followings: the largest mass 5 cm or more but less than 7 cm, three nodal sites [each ≥3 cm], no serious effusion) which is defined as to be compatible with criteria for rituximab administration. Patients aged 20–80 years with previously untreated and advanced-stage, very low tumor burden FL (grade 1-3A) were randomized to the WW arm or rituximab-induction arm (immediately initiating rituximab monotherapy [375 mg/m2, days 1, 8, 15, and 22]). Rituximab monotherapy was administered to both arms when the tumor burden was intermediate repeatedly. The primary endpoint was event-free survival (EFS), defined as follows: HTB based on the GELF criteria, initiation of cytotoxic chemotherapy and/or radiotherapy, HT, or death. Assuming a 3-year EFS of 50% in the WW arm and a 12% increase in the 3-year EFS of the rituximab induction arm, the sample size was set at 145 patients per arm with a one-sided alpha of 5%, power of 80%, an accrual period of 6.5 years, and a follow-up period of 3 years after the completion of accrual.
Results: Between December 2016 and March 2023, 292 patients from 54 hospitals in Japan were randomized as follows: 148 and 144 in the WW and rituximab induction arms, respectively. The baseline characteristics were as follows (WW vs. rituximab): median age, 65 vs. 67 years; male, 44.6% vs. 40.3%; Ann Arbor stage III/IV, 55.4/44.6% vs. 52.1/47.9%; and FLIPI low/intermediate/high risk, 13.5/50.7/35.8% vs. 16.0/45.8/38.2%, respectively. In June 2024, the Data and Safety Monitoring Committee of the JCOG recommended the early termination of the study by a pre-planned 2nd interim analysis. With a median follow-up of 2.5 years (range: 0-6.9) among all patients, EFS was significantly better in the rituximab induction arm than in the WW arm (hazard ratio, 0.625; 95% confidence interval, 0.425–0.918; one-sided log-rank P = 0.0078 < 0.0123, alpha adjusted for multiplicity). The detailed EFS events were mainly HTB and exposure to cytotoxic chemotherapy in both arms. An imbalance was observed in the number of HT events (n=18 in the WW arm versus n=9 in the rituximab arm). The 3-year progression-free and overall survival rates were 50.6% and 98.4%, respectively, in the WW arm and 49.6% and 97.3 %, respectively, in the rituximab induction arm. No significant differences were observed in the number of deaths (n=7 in each arm).
Conclusion: Rituximab induction has been confirmed to delays disease progression to HTB and the initiation of cytotoxic chemotherapy in patients with untreated advanced-stage very low tumor burden FL. We recommend the early administration of rituximab as an initial treatment approach for such patients.
Disclosures: Fukuhara: Takeda: Honoraria, Research Funding; Eisai: Honoraria; Gilead: Honoraria; Eli Lilly: Honoraria; Kyowa Kirin: Honoraria, Research Funding; LOXO Oncology: Research Funding; Genmab: Honoraria, Research Funding; Chordia Therapeutics: Research Funding; Chugai Pharma: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; AstraZeneca: Honoraria; Incyte and Takeda: Research Funding; Janssen: Honoraria; Meiji Seika: Honoraria; Nippon kayaku: Honoraria; Novartis: Honoraria; Ono: Honoraria; Soreisia: Honoraria. Maruyama: Zenyaku: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria; Takeda: Honoraria, Research Funding; Taiho: Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Symbio: Honoraria, Research Funding; Otsuka: Research Funding; Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Nippon Shinyaku: Honoraria; MSD: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; BMS: Consultancy, Honoraria, Research Funding. Ishizawa: Chugai: Honoraria; Ono: Honoraria; KyowaKirin: Honoraria. Makita: Abbvie: Honoraria; Celgene/BMS: Honoraria; Chugai: Honoraria; Genmab: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Takeda: Honoraria. Munakata: CHUGAI PHARMACEUTICAL, Janssen Pharmaceutical, ONO PHARMACEUTICAL, Kyowa Kirin, Genmab, NIPPON SHINYAKU: Research Funding; Mundipharma, Takeda Pharmaceutical, ONO PHARMACEUTICAL, Eisai, CHUGAI PHARMACEUTICAL, Bristol-Myers Squibb, AstraZeneca, NIPPON SHINYAKU, Gilead Sciences, Nippon Kayaku, MSD, Janssen Pharmaceutical, AbbVie GK, Amgen: Honoraria. Ichikawa: BeiGene: Research Funding. Miyazaki: Sumitomo Pharma: Research Funding; AstraZeneca: Honoraria; Janssen: Honoraria; Ono Pharmaceuticals: Honoraria; SymBio Pharmaceuticals: Honoraria; Zenyaku Kogyo: Research Funding; Kyowa Kirin: Honoraria, Research Funding; Novartis: Honoraria; Asahi Kasei: Honoraria; Chugai: Honoraria, Research Funding; Otsuka: Research Funding; Takeda: Research Funding; Abbvie: Honoraria; Incyte: Honoraria; Meiji Seika: Honoraria; Genmab: Honoraria; Bristol Myers Squibb: Honoraria. Takahashi: Chugai: Honoraria, Research Funding; Astellas Pharma: Research Funding; Dainihon Sumitomo: Research Funding; Eisai: Honoraria, Research Funding; SymBio Pharmaceuticals: Honoraria; Takeda: Honoraria; Mundi Pharma: Honoraria; Meiji Seika Pharma: Honoraria; Bristol Myers: Honoraria. Saito: Meiji Seika Pharma: Research Funding; IQVIA: Research Funding; Abbvie: Research Funding; Astra Zeneca: Research Funding; Nippon-shinyaku: Research Funding; Janssen Pharmaceutical KK: Research Funding. Shimada: Genmab: Honoraria; Novartis: Honoraria; AbbVie: Honoraria; Ono: Honoraria; Meiji Seika Pharma: Honoraria; Nippon Shinyaku: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Eisai: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Ohara: Consultancy; Eli Lilly: Consultancy; Jannsen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Chigai: Consultancy, Honoraria; BeiGene: Consultancy; Mundi Pharma: Honoraria; Sanofi: Honoraria. Kuroda: Bristol Myers Squibb, Pfizer, Janssen Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin, Chugai Pharmaceutical, Japan Blood Product Organization, Sumitomo Pharmaceutical, Otsuka Pharmaceutical, Asahikasei, Taiho Pharmaceutical, Mochida Pharmaceutical: Research Funding; Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, Bristol Myers Squibb, Novartis, AbbVie, Pfizer, Astellas Pharmaceutical, Nippon Shinyaku, Genmab, Pharma Essentia Japan: Honoraria; Janssen Pharmaceutical, AbbVie, Pfizer, BeiGene, Bristol Myers Squibb: Consultancy. Mishima: Bristol Myers Squibb: Research Funding; Eisai: Research Funding. Takayama: Janssen Pharmaceutical K.K.: Honoraria; AvvVie GK: Honoraria; Nippon Shinyaku Co., Ltd: Honoraria; Pfizer: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co.,Ltd: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Research Funding. Suzuki: Nippon Shinyaku: Honoraria; Meiji Seika: Honoraria; Sanofi: Honoraria. Uchida: Takeda: Honoraria; Kyowa Kirin: Honoraria; Nippon Kayaku: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Kissei: Honoraria; Asahi Kasei: Honoraria; Chugai: Honoraria; Eisai: Honoraria; Meiji Seika: Honoraria; Nippon Shinyaku: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Nakamura: Meiji Seika Pharma Co., Ltd.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Nippon Kayaku Co., Ltd.: Honoraria; Sumitomo Pharma Co., Ltd.: Honoraria; MSD: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Abbvie: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; AstraZeneca K.K.: Honoraria. Tabayashi: Janssen Pharmaceutical K.K.: Honoraria; Asahi Kasei Pharma Corporation: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Sanofi K.K.: Honoraria. Minami: Takeda: Consultancy; Pfizer: Consultancy, Speakers Bureau; Daiichi-Sankyo: Consultancy, Speakers Bureau; ONO: Research Funding; CMIC: Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy, Speakers Bureau. Dobashi: Otsuka Pharmaceutical Co., Ltd.: Research Funding; Pfizer Japan Inc: Research Funding; AbbVie GK.: Speakers Bureau; Astellas Pharma Inc.: Speakers Bureau; AstraZeneca K.K.: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; Novartis Pharma K.K.: Speakers Bureau; Amgen K.K.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Daiichi Sankyo Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd: Research Funding. Tsukasaki: Ono Pharma: Consultancy; Daiich-Sankyo: Consultancy, Honoraria, Research Funding; Meiji Seika Pharma: Consultancy, Honoraria, Research Funding; HUYABIO: Consultancy, Research Funding; Solasia Pharma: Consultancy; Yakult: Consultancy; Kyowa-hakko/Kirin: Research Funding; Yakult: Consultancy; Bristol Myers Squibb: Research Funding; Byer: Research Funding; Regeneron Pharmaceuticals Inc: Research Funding; Chugai Pharma: Honoraria; Eisai: Honoraria; Takeda: Honoraria; Sekisui Medical: Honoraria. Nagai: Abbvie: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Beigene: Research Funding; Genmab: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eli Lilly: Honoraria, Research Funding; Kyowa Kirin: Research Funding; MSD: Honoraria, Research Funding; Eisai: Honoraria; Chugai: Honoraria, Research Funding; Celgene: Research Funding; Daiichi Sankyo: Research Funding; Mitsubishi Tanabe: Research Funding; Mundi pharma: Honoraria; BMS: Honoraria; GSK: Honoraria; Meiji Seika Pharma: Honoraria; Haihe Biopharma: Research Funding; BeiGene: Honoraria; NIPPON SHINYAKU: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Solasia: Research Funding; Sumitomo Pharma: Honoraria; Takeda: Research Funding; Zenyaku Kogyo: Research Funding.