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269 Role of Allogeneic Hematopoietic Cell Transplant for Relapsed/Refractory Large B-Cell Lymphomas in the CART Era

Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Clinical Outcome: Real World Studies Based on Database Analyses
Hematology Disease Topics & Pathways:
Research, adult, Lymphomas, Clinical Research, health outcomes research, B Cell lymphoma, Diseases, real-world evidence, Lymphoid Malignancies, Adverse Events, Study Population, Human
Saturday, December 10, 2022: 3:00 PM

Alberto Mussetti1*, Leyre Bento, MD, PhD2*, Mariana Bastos-Oreiro, MD, PhD3*, Carmen Albo, MD4*, Rebeca Bailen, MD5*, Pere Barba, MD, PhD6*, Ana Benzaquén, MD7*, Javier Briones, MD, PhD8*, Ana Carolina Caballero, MD9*, António Campos, MD10*, Ignacio Español, MD, PhD11*, Christelle Ferra12*, Sebastián Garzón López13*, Pedro Antonio González Sierra, Physician14*, Luisa Maria Guerra, MD15*, Rafael Hernani, MD16*, Gloria Iacoboni, MD17*, Ana Isabel Jiminez Ubieto, MD, PhD18*, Mi Kwon, MD, PhD19*, Lucía López Corral, MD PhD20*, Oriana López-Godino, MD, PhD21*, Maria Carmen Martinez Munoz, PhD22*, Nuria Martínez-Cibrián23*, Juan Montoro Gómez, MD24*, Laura Pérez-Ortega25*, Guillermo Ortí, MD, PhD26*, Valentín Ortiz-Maldonado, MD, PhD27*, Maria-Jesús Pascual, MD28*, María Perera, MD29*, Antonio Perez, MD, PhD30*, Juan Luis Reguera, MD31*, Jose M. Sanchez, MD32*, Jaime Sanz, MD33*, Anna Torrent34*, Lucrecia Yáñez, MD, PhD35*, Rosario Varela36*, Izaksun Ceberio Echechipia, MD37*, Dolores Caballero, MD38 and Anna Sureda39

1Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet De Llobregat, Barcelona, Spain
2Hematology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain
3Servicio de Hematología y Hemoterapia, Hospital Gral. Univ. Gregorio Marañón, Madrid, Madrid, Spain
4Complejo Hospitalario de Pontevedra, Pontevedra, Spain
5Gregorio Marañón Health Research Institute, Madrid, Spain
6Department of Hematology, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
7Hematology Department, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Valencia, Spain
8Department of Hematology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
9Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
10Serviço de Transplantação de Medula Óssea, Instituto Português de Oncologia do Porto, Porto, Portugal
11Hematology Department, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
12Institut Català d´Oncologia-H. Germans Trias i Pujol, Badalona, Spain
13Hospital del SAS de Jerez, Jerez De La Frontera, Spain
14Department of Hematology, Complejo Hospitalario Universitario de Granada, Granada, Spain
15Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria, Spain
16Hematology Department, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
17Department of Hematology, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, WA, Spain
18Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Hospital Universitario 12 de Octubre, Complutense University, CNIO, Madrid, MADRID, Spain
19Department of Hematology Institute of Health Research Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain
20Department of Hematology, Hospital Clínico Universitario de Salamanca (CAUSA/IBSAL), Salamanca, Spain
21Hematology Department, Hospital Universitario Morales Meseguer, Murcia, Spain
22Hematopoietic Transplantation Unit and Hematology Department, Clinical Institute of Hematology and Oncology (ICMHO), IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain
23Hospital Clinic, Barcelona, ESP
24Hematology Department, Hospital Universitario y Politécnico la Fe, Valencia, Spain
25Hospital Universitario Virgen del Rocio, Sevilla, Spain
26HU Vall d’Hebron, Barcelona, Spain
27Department of Hematology, Hospital Clinic de Barcelona, Barcelona, Spain
28Department of Hematology, Hospital Regional Universitario de Málaga, Málaga, Spain
29Hematology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain
30Hematology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
31Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Sevilla, Spain
32Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, ESP
33Avinguda Fernando Abril Martorell, Hospital Universitario La Fe, Valencia, Valencia, Spain
34Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Research Institute. Universitat Autònoma de Barcelona, Badalona, Spain
35Hematology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain
36Hospital Universitario de A Coruna, A Coruna, ESP
37Hospital Universitario Donostia, San Sebastian, Spain
38Department of Hematology, Hospital Universitario de Salamanca (HUS/IBSAL) and CIBERONC, Salamanca, Spain
39Department of Clinical Hematology, Institut Català d’Oncologia – Hospital Duran I Reynals, IDIBELL, Barcelona, Spain

The use of anti-CD19 chimeric antigen receptor T cells (CARTS) to treat diffuse large B cell lymphomas (DLBCL) after failure of second line therapy has rapidly been adopted as the standard third-line of therapy. Salvage chemotherapy followed by allogeneic hematopoietic cell transplant (alloHCT) has been substituted even if no prospective randomized trials are available in this setting. We wanted to test the hypothesis that CARTS are at least not inferior to alloHCT, despite well-known differences between the two therapies.

We selected from the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry patients with the following characteristics: age > 18 years old; DLBCL/primary mediastinal B cell lymphoma/transformed follicular lymphoma; >2 lines of therapy; anti-CD19 CARTS or alloHCT as therapy at relapse. For the CARTS cohort: axicel or tisacel were included; infusion date within February 2019 and April 2021. For the alloHCT cohort: infusion date between January 2016 and December 2020; peripheral blood stem cell graft only; matched (> 9/10 HLA compatibility) related or unrelated and haploidentical donor only; myeloablative or reduced-intensity conditioning regimens. Observation period started from the day of cell infusion (CD34+ or CARTS) in both cohorts. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and relapse/progression (Rel/POD) of disease. Also, being alive in complete remission without moderate-severe cGVHD (cGRFS)was included to reflect severe long-term toxicity of alloHCT. Multivariate analysis was used to compensate expected differences.

A total of 316 patients (CART=215, alloHCT=101) were included into the analysis. The two cohorts of patients were significantly different in terms of baseline characteristics (table 1), especially due to characteristics of a much more aggressive and refractory disease and older age for the CARTS arm. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. For the CARTS cohort, we observed the following survival outcomes at 18 months post infusion: PFS 35% (95% CI: 29-42%), OS 46% (95% CI: 39-54%); NRM 7% (95% CI: 4-10%); Rel/POD 58% (95% CI: 52%-64%). For the alloHCT cohort: PFS 53% (95% CI: 43-62%), OS 58% (95% CI: 47-62%); NRM 28% (95% CI: 19-46%); Rel/POD 19% (95% CI: 11-27%), cGRFS 39% (95% CI: 30-49%). For the primary endopoint (PFS), multivariate analysis confirmed that CART are not inferior to alloHCT. Limiting the analysis to only patients with complete /partial response (CR/PR) (alloHCT=93, CARTS=26), no differences were reported (65% versus 55% PFS at +18 months, p=0.59, (figure 1)). Only CR/PR at infusion (hazard ratio [HR] 0.41, 95% CI=0.24-0.73, p<0.01) and ECOG>0 (HR 1.55, 95% CI=1.12-2.16, p<0.01) had a prognostic impact. However, CART had a significant impact on NRM reduction (HR 0.25, 95% CI: 0.07-0.86, p=0.02). No impact of CARTS versus alloHCT was observed for the other outcomes.

Our study showed that, despite a higher-risk population in the CARTS cohort, CARTS did not show to be inferior to alloHCT in terms of survival outcomes. Instead, we confirmed that CARTS are associated to inferior NRM. Our study, confirms that CARTS should be favored in older patients with refractory disease. However, alloHCT is still a good therapuetic strategy for patients with chemosensitive and good performance status.

Disclosures: Mussetti: BMS: Consultancy; TAKEDA: Honoraria; GILEAD: Research Funding; JAZZ PHARMACEUTICALS: Consultancy. Bastos-Oreiro: JANSSEN: Speakers Bureau; INCYTE: Consultancy, Speakers Bureau; NOVARTIS: Speakers Bureau; KITE/GILEAD: Consultancy, Honoraria; Roche: Consultancy, Research Funding, Speakers Bureau. Bailen: GILEAD: Honoraria. Barba: Allogene, Amgen, BMS, Gilead, Incyte, Jazz Pharmaceuticals, Miltenyi Biomedicine, Nektar and Novartis: Consultancy. Briones: Celgene/BMS: Research Funding; Takeda: Consultancy, Honoraria; GSK: Consultancy; Novartis: Consultancy, Honoraria; Gilead: Consultancy; BMS: Consultancy, Honoraria; HOSPITAL SANTA CREU I SANT PAU: Current Employment. Ferra: Janssen, Roche, Gilead, Takeda, Abbvie: Consultancy, Other: Medical meetings funding. Iacoboni: NOVARTIS, KITE/GILEAD, BMS/CELGENE, ASTRAZENECA, ROCHE, ABBVIE, JANSSEN, MILTENYI: Honoraria; NOVARTIS, KITE/GILEAD, BMS/CELGENE: Consultancy. Kwon: Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Gilead: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; BMS: Consultancy. Ortiz-Maldonado: KITE/GILEAD, Novartis, BMS, Janssen: Honoraria. Sureda: Astra Zeneca: Consultancy, Honoraria; Pierre Fabre: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Jannsen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; MSD: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau.

*signifies non-member of ASH