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Riedell, Peter A.

https://orcid.org/0000-0003-2719-0580

Mayo Clinic

University of Chicago

Citations 43

A Phase 1 Study of Plamotamab, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin's Lymphoma: Recommended Dose Safety/Efficacy Update and Escalation Exposure-Response Analysis
Patel, Krish , Tilly, Hervé , Ghesquières, Hervé , Collela, Jean Marc Schiano de, Chanan‐Khan, Asher , Bouabdallah, Kamal , Long, Meixiao, Clynes, Raphael , Kanodia, Jitendra , Bao, Lei , Ding, Ying , Jin, Jianhua , Ainsworth, William B., Garcha, Raman, Kye, Steve, Patel, Krish , Riedell, Peter A. , Ahmed, Sairah , Michot, Jean‐Marie , Tessoulin, Benoit , Iyengar, Sunil , Bao, Lei, Phillips, Tycel

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 9470-9472

10.1182/blood-2022-159586 Get It

CTX110 Allogeneic CRISPR-Cas9-Engineered CAR T Cells in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 1 Dose Escalation Carbon Study
Ho, Phoebe Joy, Shaughnessy, Paul , Bishop, Michael, Geethakumari, Praveen Ramakrishnan , Ross, Ainsley, Stevens, William B. , Xu, Huansheng, Ma, Anna, Beaussant-Cohen, Sarah , Bachier, Carlos, McGuirk, Joseph P. , Tam, Constantine S. , Kroger, Nicolaus , Riedell, Peter A. , Murthy, Hemant S. , Maakaron, Joseph E. , Waller, Edmund K. , Awan, Farrukh T. , Ghobadi, Armin , Piérola, Ana Alfonso , Dickinson, Michael , Stevens, William, Beaussant, Sarah cohen , Maziarz, Richard Thomas

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 10303-10306

10.1182/blood-2022-166432 Get It

PB2111: SUBGROUP ANALYSIS IN RE-MIND2, AN OBSERVATIONAL, RETROSPECTIVE COHORT STUDY OF TAFASITAMAB + LENALIDOMIDE VERSUS SYSTEMIC THERAPIES IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA
Nowakowski, Grzegorz S. , Yoon, Dok Hyun , Joffe, E., Sabatelli, L., Waltl, Eva E., Alvero, Carmelita, Hess, G., Kim, K. , Salles, G., Joffe, Erel , Zinzani, Pier Luigi , Sabatelli, Lorenzo , Hess, G., Riedell, Peter A. , Kim, K., Brixner, Diana I , Salles, G.

HemaSphere | June 24, 2022 | Volume: 6 | Issue: No issue available | Pages: 1982-1983

10.1097/01.hs9.0000851276.20930.ad Get It

Subgroup analysis in RE-MIND2, an observational, retrospective cohort study of tafasitamab plus lenalidomide versus systemic therapies in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).
Nowakowski, Grzegorz S. , Yoon, Dok Hyun , Joffe, Erel, Sabatelli, Lorenzo , Waltl, Eva E., Alvero, Carmelita, Brixner, Diana, Joffe, Erel , Zinzani, Pier Luigi , Heß, Georg , Riedell, Peter A. , Kim, Kibum , Salles, Gilles

Journal of Clinical Oncology | June 6, 2022 | Volume: 40 | Issue: 16_suppl | Pages: 7560-7560

10.1200/jco.2022.40.16_suppl.7560 Get It

7560 Background: Tafasitamab (tafa) + lenalidomide (LEN) demonstrated efficacy in adult patients (pts) with R/R DLBCL ineligible for autologous stem-cell transplant in the pivotal Phase II study L-MIND (NCT02399085) and received accelerated approval in the United States in 2020 and conditional marketing authorization in Europe and Canada in 2021 in this setting. RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared pt outcomes from L-MIND with matched pt cohorts treated with other NCCN/ESMO recommended therapies. Methods: Methodology for RE-MIND2 has been presented previously. Hypothesis-generating analyses were conducted for pt subgroups of number of extranodal sites (ENS) (0–1 vs ≥2) and elevated lactate dehydrogenase (LDH) (yes vs no) in matched cohorts of pts receiving tafa + LEN vs systemic therapies pooled (STP), polatuzumab vedotin + bendamustine + rituximab (pola-BR), rituximab + LEN (R2), and CD19 CAR-T therapies (CAR-T). The primary endpoint was overall survival (OS). Results: Of 3,454 pts enrolled, 961, 106, 106, and 149 were treated with STP, pola-BR, R2, and CAR-T, resulting in 76, 24, 33, and 37 matched pairs for pts receiving tafa + LEN, respectively. Hazard ratios (HR) for OS show a trend toward favoring tafa + LEN in most pt subgroups (Table). Conclusion: These analyses suggest that tafa + LEN may be associated with improved OS vs selected systemic therapies for certain pts with high-risk disease and may further inform physicians’ treatment choices for pts with R/R DLBCL. These analyses are not powered for statistical comparison; small sample sizes in some subgroups result in wide confidence intervals (CI) and so results must be interpreted with caution. Data for other treatment cohorts, pt subgroups, and endpoints will be presented. Funding: MorphoSys AG. Clinical trial information: NCT04697160. [Table: see text]
Primary Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) As First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma (LBCL)
Neelapu, Sattva S. , Ulrickson, Matthew L. , Thiéblemont, Catherine , Oluwole, Olalekan O. , Herrera, Alex F. , Ujjani, Chaitra S. , Kekre, Natasha , Vos, Sven de , Lui, Christine, Milletti, Francesca, Dong, Jinghui , Xu, Hairong , Oluwole, Olalekan O , Dickinson, Michael , Muñoz, Javier , Lin, Yi , Riedell, Peter A. , Chavez, Julio C

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 739-739

10.1182/blood-2021-148009 Get It

Abstract Background: High-risk LBCL is associated with poor prognosis after first-line anti-CD20 mAb-containing regimens, highlighting the need for novel treatments. Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is approved for treatment of relapsed/refractory (R/R) LBCL after ≥2 lines of systemic therapy. Here we report the primary analysis of ZUMA-12, a Phase 2, multicenter, single-arm study of axi-cel as part of first-line therapy in patients with high-risk LBCL. Methods: Eligible adults had high-risk LBCL, defined by histology (double- or triple-hit status [MYC and BCL2 and/or BCL6 translocations] per investigator) or an IPI score ≥3, plus a positive interim PET per Lugano Classification (Deauville score [DS] 4/5) after 2 cycles of an anti-CD20 mAb and anthracycline-containing regimen. Patients underwent leukapheresis and received conditioning chemotherapy (cyclophosphamide and fludarabine) followed by a single axi-cel infusion at 2×10 6 CAR T cells/kg. Non-chemotherapy bridging could be administered before conditioning per investigator discretion. The primary endpoint was investigator-assessed complete response (CR) rate per Lugano. Secondary endpoints included objective response rate (ORR; CR + partial response), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and levels of CAR T cells in blood and cytokines in serum. The primary analysis occurred after all treated patients had ≥6 months of follow-up. Results: As of May 17, 2021, 42 patients were enrolled and 40 were treated with axi-cel. Median age was 61 years (range, 23-86); 68% of patients were male, 63% had ECOG 1, 95% had stage III/IV disease, 48% had DS4, 53% had DS5, 25% had double- or triple-hit status per central assessment, and 78% had IPI score ≥3. A total of 37 patients had centrally confirmed double- or triple-hit histology or an IPI score ≥3 and were evaluable for response, with 15.9 months of median follow-up (range, 6.0-26.7). The CR rate was 78% (n=29; 95% CI, 62-90); 89% of patients had an objective response, and median time to initial response was 1 month. Among all 40 treated patients, 90% had an objective response (80% CR rate). At data cutoff, 73% of response-evaluable patients had ongoing responses. Medians for DOR, EFS, and PFS were not reached; 12-month estimates were 81%, 73%, and 75%, respectively. The estimated OS at 12 months was 91%. All 40 treated patients had AEs of any grade; 85% of patients had Grade ≥3 AEs, most commonly cytopenias (68%). Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 3 patients (8%) and 9 patients (23%), respectively. Median times to onset of CRS and NEs were 4 days (range, 1-10) and 9 days (range, 2-44), with median durations of 6 days and 7 days, respectively. All CRS and most NEs (28/29) of any grade resolved by data cutoff (1 ongoing Grade 1 tremor); 39/40 CRS events resolved by 14 days post-infusion and 19/29 NEs resolved by 21 days post-infusion. Tocilizumab was administered to 63% and 3% of patients for management of CRS or NEs, respectively; corticosteroids were administered to 35% and 33% of patients for CRS and NE management. One Grade 5 event of COVID-19 occurred (Day 350). Median peak CAR T-cell level in all treated patients was 36 cells/µL (range, 7-560), and median expansion by AUC 0-28 was 495 cells/µL × days (range, 74-4288). CAR T-cell levels peaked at a median of 8 days post-infusion (range, 8-37). Higher frequency of CCR7+CD45RA+ T cells in axi-cel product, previously associated with greater expansion of CAR T cells (Locke et al. Blood Adv. 2020), was observed in ZUMA-12, compared with the ZUMA-1 study in R/R LBCL (Neelapu et al. New Engl J Med. 2017). Conclusion: In the primary analysis of ZUMA-12, axi-cel demonstrated a high rate of rapid and complete responses in patients with high-risk LBCL, a population with high unmet need. With 15.9 months of median follow-up, responses were durable as medians for DOR, EFS, and PFS were not yet reached and over 70% of patients remained in response at data cutoff. No new safety signals were reported with axi-cel in an earlier line. Overall, axi-cel may benefit patients exposed to fewer prior therapies, and further trials in first-line high-risk LBCL are warranted to assess axi-cel in this setting. Figure 1 Figure 1. Disclosures Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria. Dickinson: Janssen: Consultancy, Honoraria; Takeda: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Celgene: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau. Munoz: Kite, a Gilead Company, Kyowa, Bayer, Pharmacyclics/Janssen, Seagen, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche.: Speakers Bureau; Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, and Millennium: Research Funding; Pharmacyclics/Abbvie, Bayer, Kite, a Gilead Company, Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa Kirin, Alexion, Fosun Kite, Innovent, Seagen, BeiGene, Debiopharm, Epizyme, Karyopharm, ADC Therapeutics, Servier, and Genmab: Consultancy, Other: advisory role; Alexion, AstraZeneca Rare Disease: Other: Study investigator; Targeted Oncology, OncView, Kyowa Kirin, Physicians' Education Resource, and Seagen: Honoraria. Thieblemont: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Oluwole: Pfizer: Consultancy; Curio Science: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Herrera: Takeda: Consultancy; Genentech: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Seagen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding; Gilead Sciences: Research Funding; Tubulis: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Karyopharm: Consultancy. Ujjani: Loxo: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; TG Therapeutics: Honoraria; Gilead: Honoraria; ACDT: Honoraria; Kite, a Gilead Company: Honoraria; Adaptive Biotechnologies: Research Funding; Atara Bio: Consultancy; AbbVie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Lin: Sorrento: Consultancy; Legend: Consultancy; Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Gamida Cell: Consultancy; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Juno: Consultancy; Vineti: Consultancy; Takeda: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Riedell: Bayer: Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Morphosys: Research Funding; Celgene/Bristol-Myers Squibb Company: Consultancy, Honoraria, Research Funding; Verastem Oncology: Honoraria; Kite, a Gilead Company: Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; BeiGene: Consultancy; Calibr: Research Funding; Xencor: Research Funding; Tessa Therapeutics: Research Funding. Kekre: Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lui: Gilead Sciences: Other: stock or other ownership; Kite, a Gilead Company: Current Employment, Other: travel support. Milletti: Kite, a Gilead company: Current Employment; Gilead Sciences: Other: stock or other ownership . Dong: Kite, a Gilead Company: Current Employment; Gilead Sciences: Other: stock or other ownership ; GliaCure/Tufts: Consultancy, Other: advisory role, Patents & Royalties. Xu: Kite, A Gilead Company: Current Employment; Gilead Sciences: Other: stock or other ownership . Chavez: MorphoSys, Bayer, Karyopharm, Kite, a Gilead Company, Novartis, Janssen, AbbVie, TeneoBio, and Pfizer: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Merk: Research Funding; AstraZeneca: Research Funding; MorphoSys, AstraZeneca, BeiGene, Genentech, Kite, a Gilead Company, and Epizyme: Speakers Bureau; BMS: Speakers Bureau.
Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation
Riedell, Peter A. , Hamadani, Mehdi , Ahn, Kwang Woo , Litovich, Carlos, Brunstein, Claudio G. , Cashen, Amanda F. , Cohen, Jonathon B. , Epperla, Narendranath , Hill, Brian T. , Im, Annie , Inwards, David J. , Lister, John , McCarty, John M. , Pingali, Sai Ravi , Shaughnessy, Paul , Solh, Melhem , Stiff, Patrick J. , Kharfan‐Dabaja, Mohamed A. , Herrera, Alex F. , Sauter, Craig S. , Smith, Sonali M. , Kharfan-Dabaja, Mohamed A , Herrera, Alex F , Hamadani, Mehdi , Epperla, Narendranath , Riedell, Peter A , Hill, Brian , Shadman, Mazyar , Vose, Julie M.

British Journal of Haematology | September 28, 2021 | Volume: 195 | Issue: 5 | Pages: 757-763

10.1111/bjh.17865 Get It

SummaryIn young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front‐line setting. Recently, time‐to‐event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post‐autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six‐month [hazard ratio (HR) = 7·68], 12‐month (HR = 6·68), and 18‐month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non‐relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high‐risk group with inferior post‐relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up‐front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.
Effect of time to relapse on overall survival (OS) in mantle cell lymphoma (MCL) patients (pts) following frontline high-dose therapy and autologous hematopoietic cell transplantation (autoHCT).
Ahn, Kwang Woo , Litovich, Carlos, Kharfan‐Dabaja, Mohamed A. , Herrera, Alex F. , Sauter, Craig S. , Smith, Sonali M. , Riedell, Peter A. , Hamadani, Mehdi

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 7521-7521

10.1200/jco.2021.39.15_suppl.7521 Get It

7521 Background: In MCL, outcomes are heterogeneous and the clinical significance of the timing of relapse following autoHCT and its impact on OS is not well defined. Using the CIBMTR database, we evaluate the effect of post-autoHCT time to relapse on OS over time. Methods: Adult MCL pts treated with up to two lines of rituximab-based induction therapy followed by first autoHCT within 1-year of diagnosis were identified between 2000-2018. Primary outcomes included OS and post-relapse OS. A dynamic landmark analysis was performed at 6-month intervals following autoHCT to evaluate the impact of relapse on OS while adjusting for significant patient- and disease-related variables. Post-relapse OS was evaluated in pts who experienced relapse. Results: Of the 461 pts included in the analysis, the median age was 60 years (range 29-78), 57% had a KPS of ≥ 90, 83% had stage III-IV disease at diagnosis, and 76% had extranodal involvement. BEAM was the most common conditioning regimen (58%) and 23% of pts received post-autoHCT maintenance rituximab. With a median follow-up of 67 months, the 5-year progression-free survival was 45.8% with a 5-year OS of 69.6%. On multivariate analysis, age ≥60 years was associated with worse OS (HR= 1.55, 95% CI 1.08-2.24, p=0.0191) at all landmark timepoints. Additionally, the impact of relapse on OS varied with time (p=0.006) and was greatest at the 6-month (HR=7.68), 12-month (HR=6.68), and 18-month (HR=5.81) landmark timepoints. The risk of death for relapsing pts decreased with time and was mirrored by an improvement in adjusted OS for both relapsing and non-relapsing pts. In total, 9.3% of patients relapsed prior to the 18-month landmark timepoint. Relapse at the 6-month, 12-month, and 18-month landmark timepoints correlated with a poor median post-relapse OS of 9 months, 24 months, and 34 months, respectively (Table). Conversely, patients relapsing after the 18-month landmark timepoint experienced a median post-relapse OS ranging from 44-67 months. Conclusions: In MCL, early relapse (< 18-months) following autoHCT defines a high-risk group with inferior post-relapse OS. This population should be considered for clinical trials or novel therapeutic approaches including early utilization of chimeric antigen receptor T-cell therapy.[Table: see text]
Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B Cell Lymphoma (LBCL)
Neelapu, Sattva S. , Ulrickson, Matthew L. , Oluwole, Olalekan O. , Herrera, Alex F. , Thiéblemont, Catherine , Ujjani, Chaitra S. , Kekre, Natasha , Vos, Sven de , Milletti, Francesca, Goyal, Lovely, Kawashima, Jun , Oluwole, Olalekan O , Dickinson, Michael , Lin, Yi , Riedell, Peter A. , Yang, Yin David , Chavez, Julio C

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 49-49

10.1182/blood-2020-134449 Get It

Background: Pts with high-risk LBCL have poor outcomes with R-CHOP chemoimmunotherapy (Sathyanarayanan, et al. ASH 2016. #106), and ≈50% of pts will not achieve long-term disease remission (Coiffier, et al. ASH Ed Program. 2016), highlighting unmet need for new therapies. Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, was approved for treatment of adults with R/R LBCL after ≥ 2 lines of systemic therapies based on the pivotal study, ZUMA-1 (Neelapu SS, et al. NEJM. 2017). ZUMA-12 is a Phase 2, multicenter, open-label, single-arm study of axi-cel as part of first-line therapy in pts with high-risk LBCL. Here, we present interim efficacy, safety, and pharmacokinetics (PK) results from ZUMA-12. Methods: Eligible adults (≥ 18 y) met 2 criteria for high-risk LBCL: i) double- or triple-hit lymphoma by fluorescent in situ hybridization per investigator or LBCL with IPI score ≥ 3; and ii) positive interim PET per Lugano Classification (Cheson, et al. J Clin Oncol. 2014; Deauville score [DS] 4 or 5) after 2 cycles of an anti-CD20 monoclonal antibody and anthracycline containing regimen, which served as a dynamic risk assessment. Pts with PMBCL were not eligible. Pts underwent leukapheresis (≥ 2 wks after prior systemic therapy) and optional non-chemotherapy bridging at investigator discretion, followed by conditioning chemotherapy (cyclophosphamide 500 mg/m2/d and fludarabine 30 mg/m2/d for 3 d) and a single axi-cel infusion (target dose, 2 × 106 CAR T cells/kg). The primary endpoint was investigator-assessed complete response (CR) rate per Lugano. Key secondary endpoints included objective response rate (ORR), frequency of adverse events (AEs), and levels of CAR T cells and cytokines in blood and serum. Results: As of July 15, 2020, 31 pts have been enrolled and treated, and as of January 24, 2020, in a planned interim analysis, 15 pts were treated with axi-cel with ≥ 3 mos of follow-up. Median age was 60 y (range, 39 - 86), 67% of pts were male, 73% had ECOG of 1, 40%/60% had DS4/5; 60% had double- or triple-hit status per investigator, and 67% had IPI score ≥ 3. Baseline characteristics were largely comparable to ZUMA-1 Cohort 1 except for lower median tumor burden in ZUMA-12 (ZUMA-1: 3897 mm2 vs ZUMA-12: 1610 mm2). Of 12 response-evaluable pts (pts with centrally confirmed high-risk LBCL who received axi-cel), the investigator-assessed ORR was 92% (95% CI, 62% - 100%) with a CR rate of 75% (95% CI, 43% - 95%); 75% of pts had ongoing responses at data cutoff. Of 15 pts treated (safety analysis set), the investigator-assessed ORR was 93% (95% CI, 68% - 100%) with a CR rate of 80% (95% CI, 52% - 96%); 86% of pts had ongoing responses at data cutoff. Of 15 safety-evaluable pts, 80% experienced Grade ≥ 3 AEs. The most common Grade ≥ 3 AEs (≥ 25% of pts) were white blood cell count decreased (40%), anemia (27%), and encephalopathy (27%). Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 20% and 27% of pts, respectively. All CRS and 10/11 NEs of any grade resolved (causally unrelated Grade 1 tremor was ongoing in 1 pt at data cutoff). Median time to onset of CRS was 4 d (range, 1 - 8), with median duration of 5 d (range, 2 - 12). Median time to onset of NEs was 9 d (range, 2 - 44), with median duration of 10 d (range, 1 - 40). Grade ≥ 3 infection was reported in 27% and Grade ≥ 3 neutrophil count decreased was reported in 20%. No Grade 5 AEs occurred. Despite similar assessment schedule and methodology, median peak CAR T cell levels were greater in ZUMA-12 vs ZUMA-1 Cohort 1 (131 cells/µL [range, 10 - 555] vs 32 cells/µL [range, 1 - 1514]). Median CAR T cell expansion (AUC0-28) was also greater in ZUMA-12 (1124 cells/µL × d [range, 147 - 4261]; ZUMA-1: 357 cells/µL × d [range, 5 - 11,507]). Median time to peak levels of CAR T cells in blood was 7 d after infusion. PK were similar in pts with double- or triple-hit lymphoma and IPI score ≥ 3. Updated safety, efficacy, and PK results will be reported, along with product characteristics and levels of key cytokines. Conclusion: ZUMA-12 is the first study evaluating CAR T cell therapy as first-line therapy in high-risk LBCL, which notably was defined by both histology and/or IPI and dynamic risk assessment with PET scan. Axi-cel demonstrated significant clinical benefit, with high ORR and CR rates and a manageable safety profile in pts for whom there is an unmet medical need. The study also provides new insights into the pharmacology of CAR T cell therapy for pts exposed to fewer prior therapies. Disclosures Neelapu: Pfizer: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; N/A: Other; Adicet Bio: Other; Poseida: Research Funding; Unum Therapeutics: Other, Research Funding; Celgene: Other: personal fees, Research Funding; Novartis: Other: personal fees; Allogene Therapeutics: Other: personal fees, Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Precision Biosciences: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Acerta: Research Funding; Karus Therapeutics: Research Funding; Cellectis: Research Funding; Legend Biotech: Other; Calibr: Other. Dickinson:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Oluwole:Spectrum Pharmaceuticals: Consultancy; Bayer: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy. Herrera:Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Karyopharm: Consultancy. Thieblemont:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bayer: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Incyte: Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Hospira: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding. Ujjani:AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Verastem Oncology: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Atara: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy. Lin:Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy; Gamida Cells: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Takeda: Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding. Riedell:Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding; Karyopharm Therapeutics: Consultancy; Bayer: Consultancy, Speakers Bureau; Kite/Gilead: Research Funding, Speakers Bureau; MorphoSys: Research Funding. Kekre:Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. de Vos:Bayer: Consultancy; Verastem: Consultancy. Yang:Kite, a Gilead Company: Current Employment. Milletti:Kite, a Gilead Company: Current Employment; Gilead Sciences: Other: stock or other ownership . Goyal:Kite, a Gilead Company: Current Employment. Kawashima:Kite, a Gilead Company: Current Employment; Gilead Sciences: Other: stock or other ownership . Chavez:Merck: Research Funding; Morphosys: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Bayer: Consultancy; BeiGene: Speakers Bureau; Karyopharm: Consultancy; AbbVie: Consultancy; Verastem: Consultancy; Pfizer: Consultancy.