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2967 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

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster II
Hematology Disease Topics & Pathways:
Diseases, Biological, Lymphoma (any), Therapies, CAR-Ts, Non-Hodgkin Lymphoma, B-Cell Lymphoma, immunotherapy, Lymphoid Malignancies
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Sattva S. Neelapu, MD1, Armin Ghobadi, MD2*, Caron A. Jacobson, MD, MMSc3*, David B. Miklos, MD, PhD4, Lazaros J. Lekakis, MD5*, Olalekan O. Oluwole, MBBS, MPH6, Yi Lin, MD, PhD7, Ira Braunschweig, MD8*, Brian T. Hill, MD, PhD9,10, John M. Timmerman, MD11, Abhinav Deol, MD12, Patrick M. Reagan, MD13, Patrick J. Stiff, MD14, Ian W. Flinn, MD, PhD15, Umar Farooq, MD16, Andre Goy, MD17, Peter A. McSweeney, MD18*, Javier Munoz, MD19, Tanya Siddiqi, MD20, Julio C. Chavez, MD21, Alex F. Herrera, MD22, Allen Xue, PhD23*, Yizhou Jiang, PhD23*, Adrian Bot, MD, PhD23*, John M. Rossi, MS23*, Jenny J. Kim, MD, MS23*, William Y. Go, MD, PhD23 and Frederick L. Locke, MD24

1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
2Washington University School of Medicine, St. Louis, MO
3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
4Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA
5University of Miami Health System, Sylvester Comprehensive Care Center, Miami, FL
6Vanderbilt-Ingram Cancer Center, Nashville, TN
7Division of Hematology, Mayo Clinic, Rochester, MN
8Department of Hematology and Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
9Taussig Cancer Institute, Department of Hematology & Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH
10Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
11UCLA David Geffen School of Medicine, Los Angeles, CA
12Department of Oncology, Blood and Marrow Stem Cell Transplant Program, Karmanos Cancer Institute/Wayne State University, Detroit, MI
13Wilmot Cancer Institute Division of Hematology/Oncology, University of Rochester Medical Center, Rochester, NY
14Loyola University Medical Center, Maywood, IL
15Sarah Cannon Research Institute, Nashville, TN
16Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
17John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ
18Colorado Blood Cancer Institute, Denver, CO
19Banner MD Anderson Cancer Center, Gilbert, AZ
20City of Hope National Medical Center, Duarte, CA
21H. Lee Moffitt Cancer Center and Research Institute, Lutz, FL
22Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
23Kite, a Gilead Company, Santa Monica, CA
24Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL

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 (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, transformed follicular lymphoma) underwent leukapheresis and received low-dose conditioning followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg (Neelapu and Locke 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. Exploratory analyses, including normal B cell levels in peripheral blood over time and frequency of use of safety interventions of interest, were 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%. The CR rate was 53% (29/55) in patients with disease refractory to ≥ 2 consecutive prior lines of therapy and 72% (18/25) in patients who had relapsed within 12 months after autologous stem cell transplantation. 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.

To investigate the relationship between B cell recovery and ongoing response, B cell levels were assessed over time. 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.

Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) were generally reversible and reported for 12% and 31% of patients, respectively. Tocilizumab (45%) and/or steroids (28%) were used for the management of CRS and NE. The use of vasopressors, dialysis, and intubation were minimal, used in only 17%, 3%, and 3% of patients, respectively.

Thirty-four percent of patients (37/108) had either no CRS/NE (6%) or only Grade 1 CRS with (12%) or without (16%) Grade 1 NE. For these 37 patients, the median onset of CRS and NE was 2 and 7 days after infusion, respectively. Patients with Grade 0 – 1 CRS/NE had similar efficacy (ORR, 86%; CR, 65%) but lower peak/AUC CAR T cell levels vs the overall population.

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.

Conclusion: High rates of durable response were observed in patients with HGBCL and double-expressor B cell lymphoma, with approximately half of these patients (18/37) maintaining CR at ≥ 1 year. Efficacy in these high-risk populations was comparable to the overall patient population in ZUMA-1. At 12 months, B-cell recovery was observed in over half the patients with ongoing remission. About one-third of patients had only Grades 0 – 1 CRS/NE yet showed comparable efficacy with the overall patient population. High-grade CRS/NE were largely managed with tocilizumab and steroids with very low use of intensive or invasive interventions. Updated outcomes with a minimum of 2 years of follow-up will be presented.

Disclosures: Neelapu: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Research Funding; Karus: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Unum Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Miklos: Adaptive Biotechnologies: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pharmacyclics - Abbot: Consultancy, Research Funding; Kite - Gilead: Consultancy, Research Funding; Genentech: Research Funding; Janssen: Consultancy, Research Funding. Hill: Amgen: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy. Reagan: Seattle Genetics: Research Funding. Flinn: Novartis: Research Funding; BeiGene: Research Funding; Seattle Genetics: Research Funding; Verastem: Consultancy, Research Funding; Curis: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Portola: Research Funding; Gilead: Research Funding; TG Therapeutics: Research Funding; Incyte: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Kite: Research Funding; ArQule: Research Funding; Agios: Research Funding; Infinity: Research Funding; Forma: Research Funding; Constellation: Research Funding; Calithera: Research Funding; Forty Seven: Research Funding; Genentech: Research Funding; Trillium: Research Funding; Verastem: Research Funding. McSweeney: Kite, a Gilead Company: Honoraria, Membership on an entity's Board of Directors or advisory committees. Munoz: Alexion: Consultancy; Genentech: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Janssen: Consultancy; Kite: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy. Siddiqi: Juno Therapeutics: Other: Steering committee; Beigene: Consultancy; Seattle Genetics: Speakers Bureau; Astra-Zeneca: Other: Advisory Board; Janssen: Speakers Bureau; Pharmacyclics: Speakers Bureau. Herrera: Bristol-Myers Squibb: Consultancy, Research Funding; KiTE Pharma: Consultancy, Research Funding; Seattle Genetics: Research Funding; Gilead Sciences: Research Funding; Genentech: Consultancy, Research Funding; Merck, Inc.: Consultancy, Research Funding; Immune Design: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Research Funding. Xue: Kite, a Gilead Company: Employment. Jiang: Kite, a Gilead Company: Employment. Bot: KITE: Employment. Rossi: KITE: Employment. Kim: Kite, a Gilead Company: Employment. Go: KITE: Employment. Locke: Cellular BioMedicine Group Inc.: Consultancy; Novartis Pharmaceuticals: Other: Scientific Advisor; Kite Pharma: Other: Scientific Advisor.

*signifies non-member of ASH