In a phase 1 trial, 43 patients with relapsed/refractory multiple myeloma were lymphodepleted, including with a CD52 immune cell-depleting antibody, and treated with ALLO-715, an allogeneic, BCMA-directed CAR T therapy with TRAC and CD52 knockouts to avoid graft–host toxicity and enhance persistence, respectively. Most patients experienced high-grade adverse events, including infections and CRS, comparable to FDA-approved anti-BCMA therapies, but no GvHD was observed. With only 5 days (median) between enrollment and treatment, CAR T cells expanded in vivo, and the majority of patients demonstrated anti-myeloma therapeutic response.
Contributed by Alex Najibi
ABSTRACT: ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen. Key secondary endpoints were response rate and duration of response. Grade ≥3 adverse events were reported in 38 (88.0%) of patients. Cytokine release syndrome was observed in 24 patients (55.8%), with 1 grade ≥3 event (2.3%) and neurotoxicity in 6 patients (14%), with no grade ≥3 events. Infections occurred in 23 patients (53.5%), with 10 (23.3%) of grade ≥3. Overall, 24 patients (55.8%) had a response. Among patients treated with 320 × 106 CAR+ T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n = 24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma.
Author Info: (1) Myeloma Service and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. mailanks@mskcc.org. Department of Medicine, Weill Cornell Medical Colle
Author Info: (1) Myeloma Service and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. mailanks@mskcc.org. Department of Medicine, Weill Cornell Medical College, New York, NY, USA. mailanks@mskcc.org. (2) Colorado Blood Cancer Institute, Denver, CO, USA. (3) Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. (4) Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA. (5) Division of Bone Marrow Transplantation and Cellular Therapy, Stanford University Hospital, Stanford, CA, USA. (6) Vanderbilt University Medical Center, Nashville, TN, USA. (7) Bone Marrow Transplant and Cellular Therapy Program, Sarah Cannon Blood Cancer Center at St. David's South Austin Medical Center, Austin, TX, USA. (8) Banner MD Anderson Cancer Center, Gilbert, AZ, USA. (9) Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA. (10) Texas Transplant Institute, San Antonio, TX, USA. (11) Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, USA. (12) Allogene Therapeutics, South San Francisco, CA, USA. (13) Allogene Therapeutics, South San Francisco, CA, USA. (14) Allogene Therapeutics, South San Francisco, CA, USA. (15) Allogene Therapeutics, South San Francisco, CA, USA. (16) Allogene Therapeutics, South San Francisco, CA, USA. (17) Allogene Therapeutics, South San Francisco, CA, USA. (18) Mayo Clinic, Rochester, MN, USA.
