Efficacy and Safety of Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor T-Cell for the Treatment of Relapsed and Refractory AL Amyloidosis
Abstract
PURPOSE The use of anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy for AL amyloidosis (AL) is limited owing to patient frailty. HBI0101 anti-BCMA CART was the first proof of concept for its applicability to AL. This report addresses the AL patient cohort treated to date within the phase Ia/Ib clinical trial (ClinicalTrials.gov identifier: NCT04720313 ). METHODS After lymphodepletion, most AL patients were infused with 800 × 10 6 CARTs. RESULTS Sixteen patients were treated, with a median of four previous lines of therapy (range, 3-10), 14/16 were triple class refractory, and 6/16 were refractory to belantamab. Most patients (13/16) had cardiac involvement, including five with MAYO stage IIIa/IIIb at study entry. Cytokine release syndrome was frequent (14/16) but mostly low grade (grade 3: 3/16, no grade 4/5). No neurologic toxicity or treatment-related deaths were observed. There were five grade 3 AL-related organ deteriorations resolved quickly with supportive care. The overall hematologic response rate was 15/16 (94%) and complete response (CR) was 12/16 (75%). Minimal residual disease negativity was achieved in 9/14 evaluable patients. Most patients (8/13 evaluable) achieved an objective organ response. Seven patients died during long-term follow-up, three while in CR/very good partial response, and the median overall survival was 10.1 months (95% CI, 5.8 to not reached). CONCLUSION This largest clinical trial of AL patients treated with anti-BCMA CART demonstrates acceptable and manageable toxicity in a highly frail and resistant population with remarkable efficacy, leading to fast organ responses. Among patients with baseline advanced cardiac disease, deaths in the first year were frequent, suggesting that this effective therapy should be considered earlier in the course of therapy. Anti-BCMA CART may become a powerful tool for improving organ function and survival in patients with AL.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (22)
Eyal Lebel
4Hadassah Medical Center, Faculty of Medicine, The Hebrew University, Department of Hematology, jerusalem, Israel
Nathalie Asherie
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Shlomit Kfir-Erenfeld
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Sigal Grisariu
2The Hebrew University, Faculty of Medicine, Jerusalem, Israel
Batia Avni
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Shlomo Elias
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Miri Assayag
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Tali Dubnikov-Sharon
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Marjorie Pick
4Hadassah Medical Center, Faculty of Medicine, The Hebrew University, Department of Hematology, jerusalem, Israel
Rivka Alexander-Shani
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Nomi Bessig
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Shlomit Herr
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Alaa Shehadeh
1Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Jerusalem, Israel
Aseel Ishtay
1Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Jerusalem, Israel
Shelly Pimienta
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Vladimir Vainstein
4Hadassah Medical Center, Faculty of Medicine, The Hebrew University, Department of Hematology, jerusalem, Israel
Eran Zimran
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Yaël Cohen
7Tel Aviv University, Tel Aviv Sourasky Medical Center & Faculty of Medical and Health Sciences, Tel Aviv, Israel
Irit Avivi
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.)...
Cyrille Cohen
5Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
Polina Stepensky
1Hadassah Medical Center, Bone Marrow Transplantation and Cellular Therapy, Jerusalem, Israel
Moshe E. Gatt
9Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel