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764 Impact of Scholar-1 Refractoriness Criteria on the Efficacy of CAR-T Therapy in Aggressive B Cell Lymphoma, Compared with Non-Refractory Patients: A Real World Geltamo/Geth Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 705. Cellular Immunotherapies: Real World Outcomes and Special Populations Treated with Cellular Therapy
Hematology Disease Topics & Pathways:
Biological therapies, Lymphomas, non-Hodgkin lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies
Monday, December 12, 2022: 10:45 AM

Mariana Bastos-Oreiro, MD, PhD1*, Antonio Gutierrez, MD, PhD2*, Gloria Iacoboni, MD3*, Lucía López Corral, MD PhD4*, Juan Luis Reguera, MD5*, Nuria Martínez-Cibrian, MD6*, María José Terol, MD PhD7*, Ana Carolina Carolina Caballero Gonzalez, MD8*, Jaime Sanz, MD9*, Luisa Maria Guerra, MD10*, Pau Abrisqueta, MD, PhD11*, Gillen Oarbeascoa, MD12*, Javier Delgado13*, Rafael Hernani, MD14*, Alberto Mussetti15*, Ana Jimenez-Ubieto, MD, PhD16*, Juan-Manuel Sancho, MD, PhD17*, Anna Sureda18, Antonio Perez, MD, PhD19*, Pere Barba, MD, PhD20*, Mi Kwon, MD, PhD21* and Alejandro Martín García-Sancho, MD, PhD22*

1Servicio de Hematología y Hemoterapia, Hospital Gral. Univ. Gregorio Marañón, Madrid, Madrid, Spain
2Hematology Department, Hospital Universitario Son Dureta, Palma, Spain
3Department of Hematology, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, WA, Spain
4Department of Hematology, Hospital Clínico Universitario de Salamanca (CAUSA/IBSAL), Salamanca, Spain
5Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Sevilla, Spain
6Hematology, Hospital Clinic Barcelona, Barcelona, Spain
7Department of Hematology, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain
8Hematology Department, Hospital de la Santa Creu i Sant Pau, BARCELONA, Spain
9Avinguda Fernando Abril Martorell, Hospital Universitario La Fe, Valencia, Valencia, Spain
10Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria, Spain
11Department of Hematology, Hospital Universitari Vall d´Hebron, Barcelona, Spain
12Department of Hematology, Hospital General Universitario Gregorio Marañón, Gregorio Marañon Health Research Institute, Madrid, Madrid, Spain
13Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío, Sevilla, Spain
14Hematology Department, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
15Department of Hematology, Hospital Duran i Reynals, Instituto Catalán de Oncología, L'Hospitalet De Llobregat, Barcelona, Spain
16GELTAMO, Hospital Doce de Octubre, Madrid, Spain
17Clinical Hematology Department, Hospital Germans Trias i Pujol, Badalona, Spain
18Institut Català d'Oncologia, Hospital Duran i Reynals. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). Universitat de Barcelona, Barcelona, Spain
19Hemato-Oncology Pediatric Service, Hospital Universitario La Paz, Madrid, Spain
20Department of Hematology, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
21Department of Hematology, Hospital General Universitario Gregorio Marañón, Gregorio Marañon Health Research Institute, Madrid, Spain
22Department of Hematology, Hospital Clínico Universitario de Salamanca, IBSAL, Salamanca, Spain

Introduction.

Chimeric antigen receptor (CAR) T-cell therapy is becoming the standard of care for patients with aggressive B cell lymphoma (ABCL), including diffuse large B-cell lymphoma (DLBCL) and high-grade B cell lymphoma (H-GBCL) pre-treated with 2 lines. We have recently reported real-world data in Spain, with efficacy results similar to those reported in the pivotal studies and other real-world experiences. It is known that patients with SCHOLAR-1 refractoriness criteria have a particularly poor prognosis with any treatment, so, the objective of this analysis is to evaluate the impact of SCHOLAR-1 refractoriness criteria on efficacy compared to non-refractory population.

Methods

This is a multicenter, retrospective, observational study that included all patients with relapsed or refractory (R/R) ABCL treated with CAR-T therapy in Spain and registered in the GELTAMO/GETH database (n=404). The main objective was to analyze efficacy in terms of response rates and survival for ABCL patients with or without SCHOLAR-1 criteria (primary refractoriness, refractoriness to last treatment, or early relapse after autologous stem-cell transplant [SCT]), comparing both commercial products axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel).

Results

From the 404 patients with ABCL registered, 20 were excluded due to absence of follow-up data and 31 for primary mediastinal lymphoma histology; finally, 353 patients were included for the primary analysis; 324 (91%) received the CAR-T cell infusion (164 axi-cel and 160 tisa-cel). Patient characteristics at infusion were balanced for both CAR-T products except for younger age (57 [23-79] vs 63 [23-79], p=0.02) and more patients with bulky disease (73 [46%] vs 43 [28%], p= 0.001) in the axi-cel group. With a median follow-up from infusion of 12.2 months (95%CI:11.3-13), median progression-free survival (PFS) was 3.3 months (95%CI: 2.4-4.2), and median overall survival (OS) was 15.2 months (95%CI: 10.7-19.7) for the whole infused cohort. For the infused patients 285 (88%) met at least one SCHOLAR-1 criteria (146 [52%] axi-cel y 139 [48%] tisa-cel) and 39 (11%) were non-refractory (18 [46%] axi-cel y 21 [54%] tisa-cel). There were no significant differences in patient characteristics between SCHOLAR-1 and non-refractory groups, except for a higher rate of bulky disease in the SCHOLAR-1 patients (39% vs 9%, p=0.001). Median OS was 12.3 months (95%CI: 9-15.6) and median PFS was 3.2 months (95%CI: 2.7-3.8) in the refractory group, whereas median OS and PFS were not reached (1 year-OS: 81%; 1 year-PFS: 54%) in the non-refractory group. In the SCHOLAR-1 group, comparing axi-cel and tisa-cel, 1 year-PFS was 42% and 25% (p=0.005) (Figure 1), and 1 year-OS was 60% and 39% (p=0.001), respectively. For non-refractory patients, 1 year-PFS was 87% and 77% (p=0.37) (Figure 1) and 1 year OS was 64% and 42% (p=0.35) for axi-cel and tisa-cel, respectively. In the multivariate analysis for the Sholar-1 cohort, factors independently influencing PFS were: CAR-T tisa-cel (HR 1.7 [CI:1.23-2.34, p=02001]), having received bridging therapy (HR 1.72 [CI: 1.08-1.27, p= 0.22], refractoriness to last treatment (HR 2.04 [CI: 1-17-3.55]), HCTCI ≥2 pre-infusion (HR 1.6 [CI: 1.19-2.29]), and for OS: CAR-T tisa-cel ( HR 1.74 [CI: 1.12-2.7, p= 0.012]), ECOG ≥2 pre-apheresis ( HR 2.4 [CI:1.11-5-47, p= 0.02]), previous auto-SCT ( HR 2.22 [CI:1.4-3.52, p= 0.001]). In terms of toxicity, 82% of patients had cytokine release syndrome (CRS) (6% ≥ grade 3), and 33% of patients had Immune effector cell-associated neurotoxicity syndrome (ICANS) (11% ≥ grade 3). Rates of CRS and ICANS were no different between refractory and non-refractory patients. CRS rate was 71% and 93% and CRS ≥ grade 3 rate was 4% and 8% (p=0.001) for tisa-cel and axi-cel respectively. ICANS rate was 16% and 50%, and ICANS ≥ grade 3 rate was 4% and 18% (p=0.001), respectively. Non-relapse mortality was 5% and 7% for tisa-cel and axi-cel respectively (p= 0.64).

Conclusions:

We conclude that SCHOLAR-1 refractoriness criteria influence notably the CAR-T cell therapy efficacy. In our experience, axi-cel showed better results in terms of efficacy than tisa-cel for this population, but also significantly more toxicity. Results for non-refractory patients are significantly better with both products, but the small sample size prevents reaching solid conclusions in this population.

Disclosures: Bastos-Oreiro: INCYTE: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; KITE/GILEAD: Consultancy, Honoraria; NOVARTIS: Speakers Bureau; JANSSEN: Speakers Bureau. Iacoboni: NOVARTIS, KITE/GILEAD, BMS/CELGENE: Consultancy; NOVARTIS, KITE/GILEAD, BMS/CELGENE, ASTRAZENECA, ROCHE, ABBVIE, JANSSEN, MILTENYI: Honoraria. Terol: Janssen, Abbvie, Roche, Takeda, Astra-Zeneca: Consultancy. Abrisqueta: Incyte: Consultancy; Sandoz: Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Mussetti: GILEAD: Research Funding; BMS: Consultancy; JAZZ PHARMACEUTICALS: Consultancy; TAKEDA: Honoraria. Jimenez-Ubieto: Novartis: Consultancy. Sancho: Miltenyi Biomedicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Kern Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, 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; Eli Lilly & Company: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sureda: TAKEDA: Consultancy, Honoraria, Speakers Bureau; JANSSEN: Consultancy, Honoraria; BMS: Consultancy, Honoraria; MSD: Honoraria; ROCHE: Consultancy, Honoraria; SANOFI: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria; GILEAD: Consultancy. Barba: Allogene, Amgen, BMS, Gilead, Incyte, Jazz Pharmaceuticals, Miltenyi Biomedicine, Nektar and Novartis: Consultancy. Martín García-Sancho: Servier: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Gilead/Kite: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Eusa Pharma: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Clinigen: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Kyowa Kirin: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Incyte: Consultancy, Other: Support for attending meetings and/or travel; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Roche: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Lilly: Consultancy, Other: Support for attending meetings and/or travel; Takeda: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Miltenyi: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; ADC Therapeutics America: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Kern: Consultancy, Honoraria, Other: Support for attending meetings and/or travel.

*signifies non-member of ASH