Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma

Summary

The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Timeline

Start

2018-01-25

Primary completion

2021-03-18

Completion

2024-11-25

Outcome

Met primary endpoint

registry analysis (superiority test); Axicabtagene Ciloleucel vs Standard of Care Therapy; p <0.0001; Hazard Ratio (HR) 0.398 (95% CI 0.308 to 0.514) NCT03391466 ↗

release “results from the primary analysis of ZUMA-7 were recently reported and showed superiority of Yescarta compared to standard of care (SOC)” gilead.com ↗

release “With a median follow-up of two years, the study met the primary endpoint of event-free survival (EFS; hazard ratio 0.398, p <0.0001).” gilead.com ↗

release “ZUMA-7 Study Demonstrated Patients on Yescarta Were 2.5 Times More Likely to Be Alive at Two Years Without Cancer Progression” gilead.com ↗

release “In the ZUMA-7 sub-analysis of patients aged 65 and older, the primary endpoint of event-free survival (EFS) demonstrated that Yescarta (n=51) was superior to SOC” gilead.com ↗

release “Based on Landmark ZUMA-7 Study, Patients with DLBCL Treated Second-Line with Yescarta Had Event-Free Survival of 8.3 Months versus Two Months for SOC” gilead.com ↗

release “the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001)” gilead.com ↗

release “ZUMA-7 demonstrated that axi-cel is superior to standard of care across common prognostic subgroups, including tumor burden” gilead.com ↗

release “Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.0001)” gilead.com ↗

Publications

• Background Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
• Background Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90. doi: 10.1182/blood-2016-01-643569. Epub 2016 Mar 15.
• Background Elsawy M, Chavez JC, Avivi I, Larouche JF, Wannesson L, Cwynarski K, Osman K, Davison K, Rudzki JD, Dahiya S, Dorritie K, Jaglowski S, Radford J, Morschhauser F, Cunningham D, Martin Garcia-Sancho A, Tzachanis D, Ulrickson ML, Karmali R, Kekre N, Thieblemont C, Enblad G, Dreger P, Malladi R, Joshi N, Wang WJ, Solem CT, Snider JT, Cheng P, To C, Kersten MJ. Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma. Blood. 2022 Nov 24;140(21):2248-2260. doi: 10.1182/blood.2022015478.
• Background Kersten MJ, Qiao Y, Shah R, Solem C, Snider JT, To C, Cheng P, Spooner C, Perales MA. Quality-Adjusted Time without Symptoms or Toxicity: Analysis of Axicabtagene Ciloleucel versus Standard of Care in Patients with Relapsed/Refractory Large B Cell Lymphoma. Transplant Cell Ther. 2023 May;29(5):335.e1-335.e8. doi: 10.1016/j.jtct.2023.01.008. Epub 2023 Jan 14.
• Background Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Munoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. doi: 10.1056/NEJMoa2116133. Epub 2021 Dec 11.
• Background Westin JR, Locke FL, Dickinson M, Ghobadi A, Elsawy M, van Meerten T, Miklos DB, Ulrickson ML, Perales MA, Farooq U, Wannesson L, Leslie L, Kersten MJ, Jacobson CA, Pagel JM, Wulf G, Johnston P, Rapoport AP, Du L, Vardhanabhuti S, Filosto S, Shah J, Snider JT, Cheng P, To C, Oluwole OO, Sureda A. Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma. Clin Cancer Res. 2023 May 15;29(10):1894-1905. doi: 10.1158/1078-0432.CCR-22-3136.
• Background Westin JR, Oluwole OO, Kersten MJ, Miklos DB, Perales MA, Ghobadi A, Rapoport AP, Sureda A, Jacobson CA, Farooq U, van Meerten T, Ulrickson M, Elsawy M, Leslie LA, Chaganti S, Dickinson M, Dorritie K, Reagan PM, McGuirk J, Song KW, Riedell PA, Minnema MC, Yang Y, Vardhanabhuti S, Filosto S, Cheng P, Shahani SA, Schupp M, To C, Locke FL; ZUMA-7 Investigators; Kite Members. Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. N Engl J Med. 2023 Jul 13;389(2):148-157. doi: 10.1056/NEJMoa2301665. Epub 2023 Jun 5.
• Background Filosto S, Vardhanabhuti S, Canales M, Poiré X, Lekakis LJ, de Vos S, et al. Product attributes of axicabtagene ciloleucel (axi-cel) that associate differentially with efficacy and toxicity in second-line large B-cell lymphoma. Cancer Res. 2022;82(12_Supplement):CT004.
• Background Ghobadi A, Munoz J, Westin J, Locke FL, Miklos DB, Rapoport AP, et al. Outcomes of Subsequent Anti-Lymphoma Therapies in Patients (Pts) with Large B-Cell Lymphoma (LBCL) Treated with Axicabtagene Ciloleucel (Axi-Cel) or Standard of Care (SOC) in the Second-Line (2L) ZUMA-7 Study. Blood. 2022;140(Supplement 1):1595-1597.
• Background Locke FL, Oluwole OO, Kuruvilla J, Thieblemont C, Morschhauser F, Salles G, et al. Association of Metabolic Tumor Volume (MTV) and Clinical Outcomes in Second-Line (2L) Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Following Axicabtagene Ciloleucel (Axi-Cel) Versus Standard-of-Care (SOC) Therapy in ZUMA-7. Blood. 2022;140(Supplement 1):638-640.
• Background Chartier M, Filosto S, Peyret T, Chiney M, Milletti F, Budka J, Ndi A, Dong J, Vardhanabhuti S, Mao D, Duffull S, Dodds M, Shen R. Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma. Clin Pharmacokinet. 2024 Sep;63(9):1283-1299. doi: 10.1007/s40262-024-01413-z. Epub 2024 Sep 6.
• Background Filosto S, Vardhanabhuti S, Canales MA, Poire X, Lekakis LJ, de Vos S, Portell CA, Wang Z, To C, Schupp M, Poddar S, Trinh T, Warren CM, Aguilar EG, Budka J, Cheng P, Chou J, Bot A, Shen RR, Westin JR. Product Attributes of CAR T-cell Therapy Differentially Associate with Efficacy and Toxicity in Second-line Large B-cell Lymphoma (ZUMA-7). Blood Cancer Discov. 2024 Jan 8;5(1):21-33. doi: 10.1158/2643-3230.BCD-23-0112.
• Background Ghobadi A, Munoz J, Westin JR, Locke FL, Miklos DB, Rapoport AP, Perales MA, Reagan PM, McGuirk J, Jacobson CA, Kersten MJ, Avivi I, Peng A, Schupp M, To C, Oluwole OO. Outcomes of subsequent antilymphoma therapies after second-line axicabtagene ciloleucel or standard of care in ZUMA-7. Blood Adv. 2024 Jun 11;8(11):2982-2990. doi: 10.1182/bloodadvances.2023011532.
• Background Locke FL, Chou J, Vardhanabhuti S, Perbost R, Dreger P, Hill BT, et al. Association of pretreatment (preTx) tumor characteristics and clinical outcomes following second-line (2L) axicabtagene ciloleucel (axi-cel) versus standard of care (SOC) in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). J Clin Oncol.2022;40(16_suppl):7565
• Background Locke FL, Filosto S, Chou J, Vardhanabhuti S, Perbost R, Dreger P, Hill BT, Lee C, Zinzani PL, Kroger N, Lopez-Guillermo A, Greinix H, Zhang W, Tiwari G, Budka J, Marincola FM, To C, Mattie M, Schupp M, Cheng P, Bot A, Shen R, Bedognetti D, Miao H, Galon J. Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma. Nat Med. 2024 Feb;30(2):507-518. doi: 10.1038/s41591-023-02754-1. Epub 2024 Jan 17.
• Background Locke FL, Oluwole OO, Kuruvilla J, Thieblemont C, Morschhauser F, Salles G, Rowe SP, Vardhanabhuti S, Winters J, Filosto S, To C, Cheng P, Schupp M, Korn R, Kersten MJ. Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume. Blood. 2024 Jun 13;143(24):2464-2473. doi: 10.1182/blood.2023021620.
• Background Lunning MA, Wang HL, Hu ZH, Locke FL, Siddiqi T, Jacobson CA, Ahmed S, Miklos DB, Lin Y, Hill BT, Ghobadi A, Neelapu SS, Westin J, Dieyi C, Field P, Miao H, Shahani SA, Patel A, Spooner C, Fu C, Muramoto D, Xu H, Pasquini MC. Benefit of axicabtagene ciloleucel versus chemoimmunotherapy in older patients and/or patients with poor ECOG performance status with relapsed or refractory large B-cell lymphoma after 2 or more lines of prior therapy. Am J Hematol. 2024 May;99(5):880-889. doi: 10.1002/ajh.27283. Epub 2024 Mar 19.
• Background Tian Y, Budka J, Locke FL, Westin JR, To C, Tiwari G, Mao D, Bedognetti D, Shen RR, Andrade J, Filosto S. Tumor gene expression signatures associated with outcome in large B-cell lymphoma treated with CD19-directed CAR T-cell therapy (axicabtagene ciloleucel). Front Oncol. 2025 Feb 27;15:1519473. doi: 10.3389/fonc.2025.1519473. eCollection 2025.
• Locke FL, Siddiqi T, Jacobson CA, Ghobadi A, Ahmed S, Miklos DB, Perales MA, Munoz J, Fingrut WB, Pennisi M, Gauthier J, Shadman M, Gowda L, Mirza AS, Abid MB, Hong S, Majhail NS, Kharfan-Dabaja MA, Khurana A, Badar T, Lin Y, Bennani NN, Herr MM, Hu ZH, Wang HL, Baer A, Baro E, Miao H, Spooner C, Xu H, Pasquini MC. Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity. Blood. 2024 Jun 27;143(26):2722-2734. doi: 10.1182/blood.2023023447.
• The Lancet Haematology. The role of conferences in tackling inequalities. Lancet Haematol. 2022 Feb;9(2):e81. doi: 10.1016/S2352-3026(22)00008-4. No abstract available.
• Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.
• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
• Thiruvengadam SK, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Axicabtagene Ciloleucel	Cell therapy	2e+06 cells/kg	Intravenous
Comparator	Carboplatin	Small molecule	—	—
Comparator	Cisplatin	Other / unclassified	25 mg/m2	—
Comparator	Cisplatin	Other / unclassified	75 mg/m2	—
Comparator	Cisplatin	Other / unclassified	100 mg/m2	—
Background	Cyclophosphamide	Other / unclassified	500 mg/m2	Intravenous
Comparator	Cytarabine	Small molecule	2 g	—
Comparator	Dexamethasone	Small molecule	40 mg	—
Comparator	Etoposide	Small molecule	40 mg/m2	—
Comparator	Etoposide	Small molecule	100 mg/m2	—
Background	Fludarabine	Small molecule	30 mg/m2	Intravenous
Comparator	Gemcitabine	Small molecule	1 g	—
Comparator	Ifosfamide	Small molecule	5 g	—
Comparator	Methylprednisolone	Other / unclassified	500 mg	—
Comparator	Oxaliplatin	Small molecule	100 mg/m2	—
Comparator	Rituximab	Monoclonal antibody	375 mg/m2	—

Indications