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2117 Real-World Evidence of Tisagenlecleucel for the Treatment of Relapsed or Refractory Large B-Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster II
Hematology Disease Topics & Pathways:
Biological, CRS, Adult, Diseases, neurotoxicity, Therapies, CAR-Ts, Non-Hodgkin Lymphoma, Adverse Events, DLBCL, Lymphoid Malignancies, Study Population, Clinically relevant
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Gloria Iacoboni, MD1,2,3*, Josu Iraola-Truchuelo3*, Nuria Martinez-Cibrian, MD4*, Rebeca Bailén, MD5,6*, Lucia Lopez Corral, PhD, MD7,8*, Jose M. Sanchez, MD9*, Manuel Guerreiro, MD10*, ANA Carolina Carolina CABALLERO González11,12*, Alberto Mussetti, MD13,14*, Juan-Manuel Sancho, MD, PhD15*, Rafael Hernani, MD16,17*, Carlos Solano, MD, PhD17,18,19, Anna Sureda Balari, MD, PhD13*, Javier Briones, MD, PhD20*, Alejandro Martin Garcia-Sancho, MD, PhD7*, Mi Kwon, MD, PhD5,6*, Juan Luis Reguera, MD, PhD4* and Pere Barba, MD, PhD1,2,3*

1Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain
2Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
3Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
4Department of Hematology, University Hospital Virgen del Rocio, Sevilla, Spain
5Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
6Gregorio Marañón Health Research Institute (IiSGM), Madrid, Spain
7Hematology Department, Hospital Clínico Universitario de Salamanca, IBSAL, Salamanca, Spain
8Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain
9Hospital 12 de Octubre, Madrid, ESP
10Department of Hematology, Hospital La Fe, Valencia, Spain
11Josep Carreras Leukaemia Research Institute, Barcelona, Spain
12Hematology Department, Hospital de la Santa Creu i Sant Pau, BARCELONA, Spain
13Hematology Department, Institut Catala d'Oncologia, Hospital Duran i Reynals, L'Hospitalet De Llobregat, Spain
14Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet De Llobregat, Barcelona, Spain
15Hematology Department, ICO-IJC Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
16Department of Hematology, Hospital Clínico Universitario de Valencia, Valencia, Spain
17Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
18Department of Medicine, University of Valencia, Valencia, Spain
19Hematology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
20Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain


Tisagenlecleucel (tisa-cel) is a second generation, CD19-targeted Chimeric Antigen Receptor (CAR) T-cell therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). The pivotal phase 2 trial JULIET included 93 patients and reported an overall response rate (ORR) of 52% and a complete response rate of 40% among treated patients. However, very little is known regarding its safety and efficacy in the commercial or real-world setting as well as from an intention-to-treat perspective. In our study, we report clinical outcomes of patients with R/R LBCL treated with commercial tisa-cel in 10 Spanish institutions.


Data were collected retrospectively from all consecutive patients with R/R LBCL who underwent apheresis for tisa-cel at a Spanish site from December 2018 until June 2020. Evaluable patients included those who received a CAR-T infusion and had at least 1 month of follow-up. Adverse events after infusion were graded according to the ASTCT consensus and efficacy outcomes were assessed according to the Lugano criteria. Efficacy outcomes were calculated in the patients who received a CAR T-cell infusion and in all patients who underwent apheresis for tisa-cel (intention-to-treat).


During the study period 91 patients with R/R LBCL underwent apheresis for tisa-cel. At the study cutoff, 69 (76%) patients had received a CAR T-cell infusion whereas 22 (24%) had not due to progressive disease (n=10, 45%), pending manufacturing process (n=7, 32%), out of specification (OOS) or manufacturing failure (n=4, 18%), or others (n=1, 5%). Sixty-one patients had at least the first disease response evaluation at 1-month post-infusion. Baseline characteristics of the whole cohort and the infused patients are summarized in Table 1. Among infused patients, median age was 57 years (range 24-77) and 65% were male. Most of the patients had a high-risk International Prognostic Index score (62%), an advanced stage at diagnosis (91%) and were refractory to the previous therapy (80%). Median follow-up after CAR T-cell infusion was 4 months (1-16).

Fifty-six patients (81%) received bridging therapy before infusion, including chemotherapy in most cases (n=51, 91%). All patients received fludarabine and cyclophosphamide as lymphodepleting chemotherapy. Median time from apheresis to infusion was 53 days (range 29-225). Median infused cell dose was 2.2 x 108 CAR positive viable T-cells (range 0.4-4.2 x 108). Eleven (16%) products were considered OOS although 45% of them were infused.

Among the infused patients, 47 (68%) and 9 (13%) developed any grade of cytokine release syndrome (CRS) and neurotoxicity, respectively. Grade >2 CRS and neurotoxicity events occurred in 3 (4%) and 0 patients, respectively. Tocilizumab was administered to 21 (30%) patients and steroids to 13 (19%) patients. Nine (13%) patients required admission to the Intensive Care Unit. By day 100, 2 (3%) patients experienced non-relapse mortality. Other adverse events including infections and tumor lysis syndrome are summarized in table 2.

Best response achieved among the infused patients included complete remission in 17 (28%) patients and partial remission in 22 (36%) patients, with an ORR of 64%. Stable disease and progressive disease were the best response in 4 (7%) and 18 (29%) patients, respectively. Considering all patients who underwent apheresis, CR and PR were obtained in 19% and 24% (ORR 43%), respectively.

Median progression-free survival (PFS) and overall survival (OS) for infused patients were 3 months (95%CI 2.1-3.4) and 8 months (95%CI 5.7-10.8), respectively. In the univariate analysis, patients with ECOG score >1 (HR 4.3 95%CI 1.5 - 40.9) (p < 0.001) and IPI score >2 (HR 4.8 95%CI 1.6 – 14.4) (p = 0.002) were associated with lower PFS while an ECOG score >1 was also associated with lower OS (HR 3.4 95%CI 1.15 – 34.4) (p = 0.04). In the intention-to-treat analysis for all patients who underwent apheresis, median PFS and OS from apheresis were 4 months (95%CI 2.8-5.8) and 9 months (95%CI 5.8-11.8), respectively.


Treatment with tisa-cel was able to induce disease response with a good toxicity profile in a population of patients with LBCL treated in a European country. Poor performance status at the time of CAR T-cell infusion was associated with lower PFS and OS.

Disclosures: Iacoboni: Novartis, Gilead, Celgene, Roche: Honoraria. Guerreiro: Novartis: Honoraria. Mussetti: Novartis, Gilead: Honoraria, Research Funding. Sancho: Roche, Janssen, Celgene, Novartis, Gilead, Sandoz, Mundipharma y Takeda; Advisory y/o consultor para Roche, Janssen, Celgene, Novartis, Gilead, Sandoz, Celltrion y Kern-Pharma.: Honoraria. Hernani: Gilead: Honoraria. Sureda Balari: Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Celgene: Consultancy, Honoraria; BMS: Speakers Bureau; Roche: Honoraria. Martin Garcia-Sancho: Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy; Roche, Celgene, Janssen, Servier, Gilead: Honoraria. Kwon: Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Reguera: Celgene, Novartis: Consultancy; Novartis, Gilead: Honoraria. Barba: Novartis, Celgene, Gilead, Pfizer, Amgen, Roche: Honoraria.

*signifies non-member of ASH