Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR-T) for relapsed/refractory large B-cell lymphoma (CRC01-01)
Abstract
Anbalcabtagene autoleucel (Anbal-cel) is a CD19-directed CAR T-cell therapy incorporating dual PD-1 and TIGIT knockdown to enhance antitumor function and durability. We report the results of a Phase 1/2 study in patients with relapsed or refractory large B-cell lymphoma (LBCL). In Phase 2, 79 patients received Anbal-cel, and efficacy was evaluated in 73 patients. The complete response (CR) and partial response (PR) rates were 67.1% and 8.2%, respectively. Median progression-free survival (PFS) was 6.04 months (95% CI, 4.34-16.46), and the 6-, 12-, and 18-month PFS rates were 50.9%, 41.1%, and 35.2%, respectively. Median overall survival (OS) was not reached, with 12- and 18-month OS rates of 66.6% and 57.3%. CAR T-cell expansion was significantly greater in responders than in non-responders (median Cmax: 20,403 vs. 8,580 copies/μg). Patients were categorized into long-term response (LR) group or non-LR group based on sustained CR at 6 months. Reduced PD-1 and TIGIT expression on CAR-positive T cells was observed in LR group. Most patients (97.5%) experienced grade ≥3 adverse events, most commonly neutropenia (93.7%), followed by thrombocytopenia (41.8%) and anemia (30.4%). Cytokine release syndrome and neurologic events occurred in 57.0% and 13.9% of patients, respectively. Grade 3 CRS occurred in 8.9% of patients, with no grade 4 events reported, and grade ≥3 neurologic events occurred in 3.8%. Serious infections occurred in 25.3% of patients, and grade 5 infection was reported in 3 patients. This trial was registered at Clinicaltrials.gov (NCT04836507).
Article Details
Authors (20)
Won Seog Kim
Seok Jin Kim
Dok Hyun Yoon
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Hyungwoo Cho
Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of
Sang Eun Yoon
Deok Hwan Yang
Chonnam National University Hwasun Hospital, Jeollanam-do, Korea, Republic of
Ho-jin Shin
Pusan National University Hospital, Busan, Korea, Republic of
Hyeon-Seok Eom
National Cancer Center, Goyang, Gyeonggi, Korea, Republic of
Eunyoung Lee
Department of Medical Physiology, Graduate School of Medicine, Research Institute of Disaster Medicine, Chiba University
Ja Min Byun
Seoul National University Hospital, Seoul, Korea, Republic of
Youngil Koh
Seoul National University Hospital, Seoul National University, Jongno-gu, Seoul, South Korea
Hyewon Lee
Jongheon Jung
National Cancer Center, Korea, Goyang-Si, Gyunggi-Do, Korea, Republic of
Sung-Soo Yoon
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Ga-Young Song
Chonnam National University Hwasun Hospital, Jeollanam-do, Korea, Republic of
Do Young Kim
Juyeon Hong
Yoon Park
Korea Institute of Science and Technology (KIST), Seoul, Korea, Republic of
Songhee Han
Curocell Inc., Daejeon, Korea, Republic of
Su-Hee Cho
Curocell Inc., Daejeon, Korea, Republic of