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886 Prognostic Value of Early PET in Patients with Aggressive Non-Hodgkin Lymphoma Treated with Anti-CD19 CAR T-Cell Therapy

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Real World evidence for CAR-T Management II
Hematology Disease Topics & Pathways:
Adults, Biological, Non-Hodgkin Lymphoma, Lymphomas, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinically Relevant, Diseases, Therapies, Lymphoid Malignancies, Study Population
Monday, December 13, 2021: 7:00 PM

Jennifer L. Crombie, MD1, Robert A. Redd, MS2*, Victor A. Chow, MD3, Jordan Gauthier, MD4, Erin Mullane, DNP5*, Geoffrey Shouse, PhD6, Alex F. Herrera, MD7, Jason Romancik, MD8*, Jonathon B. Cohen, MD, MS9, Anna Saucier10*, Roch Houot, MD, PhD11*, Caron Jacobson, MD12, Philippe Armand, MD, PhD1 and Brian T. Hess, MD13

1Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, MA
2Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
3Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
4Clinical Research Division, Fred Hutchinson Cancer Research Ctr., Seattle, WA
5Seattle Cancer Care Alliance, Seattle, WA
6Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA
7City of Hope, Duarte, CA
8Winship Cancer Institute, Emory University, Atlanta, GA
9Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
10Dana Farber Cancer Institute, Boston, MA
11University Hospital of Rennes, Rennes, FRA
12Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA
13Hollings Cancer Center, Medical University of South Carolina, Charleston, SC

Introduction: Although anti-CD19 autologous chimeric antigen receptor (CAR) T-cell therapy has transformed the management of relapsed/refractory non-Hodgkin lymphoma (NHL), the majority of patients will ultimately relapse. The prognostic implications of early (1-month) metabolic response on ultimate outcome are still poorly defined, yet would have significant implications on the development of consolidation strategies.

Methods: We conducted a multi-center, retrospective study of patients with NHL who received commercial anti-CD19 CAR T-cell therapy at 5 academic medical centers between 7/2018-5/2021. All patients had a PET scan 30 (+/- 15) days following CAR T-cell infusion. Imaging responses were per investigator assessment using Lugano criteria. Cox proportional hazards models were used to identify predictors of progression free survival (PFS).

Results: A total of 193 patients were identified who received axicabtagene ciloleucel (axi-cel, n=180) or tisagenlecleucel (tisa-cel, n=13). Histologies included diffuse large B-cell lymphoma (DLBCL), NOS, n= 134 (69%), DLBCL transformed from an indolent lymphoma, n=47 (24%), primary mediastinal B-cell lymphoma (PMBCL), n=8 (4%), and Richter’s syndrome (RS), n=4 (2%). The median age was 62 (range 19-80) years; 66% of patients were male; IPI was low in 28%, intermediate in 27%, and high in 42%; median prior therapies was 3 (range 1-9); 44% had an elevated LDH prior to lymphodepletion; 30% had an elevated CRP prior to CAR T-cell infusion; 10% had bulky disease (≥10 cm) prior to lymphodepleting therapy; and 40% received bridging therapy.

The median follow-up of the entire cohort was 22 months (m). Responses at 1m included complete response (CR), n= 101 (52%), partial response (PR), n=53 (27%), stable disease (SD), n=4 (2%), and progressive disease (PD), n=35 (18%). The median PFS of the entire cohort was 11m (95% CI: 6-not reached) (Figure 1B) and median overall survival (OS) was not reached. PFS for the entire cohort was 57% (95% CI: 50-65) at 6m and 49% (95% CI: 42-58) at 12m; and OS was 79% (95% CI: 73-85) at 6m and 67% (95% CI: 61-75) at 12m. The 12m PFS and OS for patients with CR at 1m was 70% (95% CI: 61-80) and 82% (95% CI: 74-91), respectively, and was 38% (95% CI: 26-55) and 69% (95% CI: 57-84) for patients with PR/SD (Figure 1C). The 12m PFS and OS based on 1m PET (Figure 1D) was 72% (95% CI: 61-85) and 82% (95% CI: 72-93), respectively, for Deauville 1/2, 68% (95% CI: 53-88%) and 82% (CI: 69-98) for Deauville 3, 55% (95% CI: 39-79) and 83 (95% CI: 69-100) for Deauville 4, and 12% (95% CI: 3-46) and 56% (95% CI: 27-56) for Deauville 5 with PR/SD.

Indicators of shorter PFS across the entire cohort included elevated LDH at lymphodepletion (HR: 2.11 (95% CI: 1.41-3.16, p<0.001)), elevated CRP at CAR T-cell infusion (HR: 1.85 (95% CI: 1.22-2.8, p=0.004)), use of bridging therapy (HR: 1.8 (95% CI: 1.21-2.70, p=0.004)), and grade 3 or higher cytokine release syndrome (HR: 2.26 (95% HR: 1.23-4.17, p=0.009)). However, among patients with PR/SD at 1m, none of those clinical variables (including bulky disease, elevated LDH or CRP, high IPI, grade 3 or higher CRS or neurotoxicity, and use of tocilizumab or steroids) predicted progression at 3m. Among patients with a CR at 1m, an elevated LDH at the time of lymphodepletion correlated with an increased risk of relapse at 3m (HR: 4.14 (95% CI: 1.20-16.56, p=0.03)).

Discussion: We demonstrate that PFS is improved in patients with a CR at day +30 PET as compared to patients with a PR or SD. Furthermore, patients with Deauville 1/2 appear to have similar outcomes as those with a Deauville 3. No independent clinical variables were able to predict which patients with a PR/SD were likely to progress at the time of their next scan. Novel biomarkers such a minimal residual disease (MRD), may be necessary to further guide treatment modification in this setting.

Disclosures: Crombie: Karyopharm: Consultancy; Incyte: Consultancy; Merck: Research Funding; Abbvie: Research Funding; Bayer: Research Funding; Roche: Research Funding. Chow: AstraZeneca: Research Funding; ADC Therapeutics: Current equity holder in publicly-traded company, Research Funding. Gauthier: Eusapharma: Consultancy; Juno Therapeutics, A BMS Company: Research Funding; JMP: Consultancy; Larvol: Consultancy; Multerra Bio: Consultancy; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene, a BMS Company: Research Funding. Shouse: Beigene: Honoraria; Kite Pharma: Speakers Bureau. Herrera: Karyopharm: Consultancy; Tubulis: Consultancy; Merck: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Gilead Sciences: Research Funding; Seagen: Consultancy, Research Funding; Takeda: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding. Cohen: Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly: Research Funding; Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead: Consultancy. Jacobson: Lonza: Consultancy, Honoraria, Other: Travel support; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; Axis: Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Other: Travel support; Humanigen: Consultancy, Honoraria, Other: Travel support; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; Nkarta: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Clinical Care Options: Speakers Bureau. Armand: Merck: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Affimed: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Daiichi Sankyo: Consultancy; Miltenyi: Consultancy; Tessa Therapeutics: Consultancy; GenMab: Consultancy; C4: Consultancy; Enterome: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding; IGM: Research Funding; Kite: Research Funding; Pfizer: Consultancy; Infinity: Consultancy; Otsuka: Research Funding; Sigma Tau: Research Funding. Hess: BMS: Speakers Bureau; ADC Therapeutics: Consultancy.

*signifies non-member of ASH