2-Year Follow-up and High-Risk Subset Analysis of Zuma-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B Cell Lymphoma
Year: 2019
Type: article
Abstract: Background Axi-cel is a US FDA-approved, autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for the treatment of patients with relapsed or refractory large B cell lymphoma with ≥2 prior systemic therapies. This report focuses on high-risk patient populations as well as long-term durability of response, and B cell recovery. Methods In ZUMA-1, eligible patients with refractory large B cell lymphoma underwent leukapheresis and received low-dose conditioning followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg (Neelapu et al. NEJM. 2017; NCT02348216). Outcomes in patients with double-expressor B cell lymphoma (MYC [≥40%] and BCL-2 [≥50%] protein expression by immunohistochemistry [IHC]) or high-grade B cell lymphoma (HGBCL), defined as double- or triple-hit (MYC+ and BCL2+ and/or BCL6+ by fluorescence in situ hybridization) or not otherwise specified (MYC– and >70% Ki67 by IHC) were examined by independent pathology review. The exploratory analysis of normal B cell levels in peripheral blood over time was also performed. A long-term follow-up analysis will be conducted with a data cutoff of August 11, 2018 for all 108 patients, including the HGBCL subgroup. Results As of August 11, 2017, all 108 patients had at least 1 year of follow-up, with a median follow-up of 15.4 months. The objective response rate (ORR) was 82% with a complete response (CR) rate or 58%. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NE) were generally reversible and reported for 12% and 31% of patients, respectively. High-risk genetics were assessed in the 47 evaluable pre-treatment tumor samples: 37 patients (79%) had HGBCL or double-expressor B cell lymphoma and had an ORR of 89% (33/37) including a CR rate of 68% (25/37). Forty-two percent of patients overall had ongoing responses with a median follow-up of 15.4 months including 49% (18/37) of patients with high-risk genetics. Overall, of the 87 evaluable patients, 47% had no detectable B cells at baseline, and the remainder had levels close to or below the lower level of quantification of the assay. In patients with ongoing responses at 12 months post axi-cel infusion, 19 of the 35 (54%) patients with evaluable samples had detectable B cells at 12 months. This suggests B cell recovery in some patients with ongoing response as only 6 of 40 (15%) patients with evaluable samples had detectable B cells at 3 months after axi-cel infusion. Conclusion Patients with high-risk genetics had similar favorable outcomes as observed for the overall study population, with approximately half of these patients (18/37) maintaining CR at ≥ 1 year. At 12 months, B-cell recovery was observed in over half the patients with ongoing remission. Updated safety and efficacy results will be presented with a minimum follow-up of 2 years and a median follow-up of 27.1 months.
Authors: Sattva S. Neelapu, Armin Ghobadi, Caron A. Jacobson, David B. Miklos, Lazaros J. Lekakis, Olalekan Oluwole, Yi Lin, Ira Braunschweig, Brian T. Hill, John Timmerman, Abhinav Deol, Patrick M. Reagan, Patrick Stiff, Ian W. Flinn, Umar Farooq, Andre Goy, Peter A. McSweeney, Javier Munoz, Tanya Siddiqi, Julio C. Chavez, Alex F. Herrera, Allen Xue, Yizhou Jiang, Adrian Bot, John M. Rossi, Jenny J. Kim, William Y. Go, Frederick L. Locke
Institutions: The University of Texas MD Anderson Cancer Center, Washington University in St. Louis, Dana-Farber Cancer Institute, Stanford Medicine, Stanford University, University of Miami Health System, Sylvester Comprehensive Cancer Center, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Mayo Clinic, Albert Einstein College of Medicine, Montefiore Medical Center, Cleveland Clinic, University of California, Los Angeles, Wayne State University, The Barbara Ann Karmanos Cancer Institute, University of Rochester Medicine, Loyola University Chicago, Sarah Cannon, University of Iowa, University of Iowa Hospitals and Clinics, Hackensack University Medical Center, Colorado Blood Cancer Institute, Banner MD Anderson Cancer Center, City Of Hope National Medical Center, Moffitt Cancer Center, Kite (United States)
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2913258428