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227 The Post-CAR Prognostic Index (PC-PI): A New Prognostic Score to Predict Overall Survival in Large B-Cell Lymphoma Patients Progressing after Chimeric Antigen Receptor T-Cell Therapy

Program: Oral and Poster Abstracts
Type: Oral
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Translational Data and Prognostic Factors
Hematology Disease Topics & Pathways:
Research, Biological therapies, Lymphomas, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, real-world evidence, aggressive lymphoma, Therapies, Lymphoid Malignancies
Saturday, December 9, 2023: 3:00 PM

Gloria Iacoboni, MD1*, Victor Navarro Garces2*, Josu Iraola1*, Pierre Sesques3*, Kai Rejeski, MD4, Fabio Serpenti, MD5*, Mariana Bastos-Oreiro6*, ANA Africa Martin Lopez, MD7*, Javier Delgado, MD8*, Ariadna Perez9*, Manuel Guerreiro, MD10*, Ana Carolina Caballero Gonzalez11*, Nuria Martinez-Cibrian, MD12*, Hugo Daniel Luzardo Henriquez, MD13*, Jose Maria Sanchez Pina14*, Juan-Manuel Sancho, MD, PhD15*, Herve Ghesquieres, MD3*, Alberto Mussetti, MD16*, Pere Barba, MD1, Lucia Lopez Corral, MD, PhD7*, Rafael Hernani9*, Juan Luis Reguera, MD8*, Anna Maria Sureda Balari, MD, PhD16, Francesc Bosch, MD, PhD1*, Alejandro Martin Garcia-Sancho, MD7*, Mi Kwon17, Andrea Kuhnl5*, Marion Subklewe, MD4, Emmanuel Bachy, MD, PhD18*, Guillermo Villacampa19* and Pau Abrisqueta Costa1*

1Vall d'Hebron University Hospital, Barcelona, Spain
2Oncology Data Science (ODysSey) Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
3Lyon Sud Hospital, Lyon, France
4LMU University Hospital, Munich, Germany
5King’s College Hospital NHS Foundation Trust, London, United Kingdom
6Hospital General Universitario Gregorio Marañón, Madrid, Spain
7Hospital Universitario de Salamanca, Salamanca, Spain
8University Hospital Virgen del Rocío, Sevilla, Spain
9Hospital Clínico Universitario, Valencia, Spain
10Hospital Universitario La Fe, Valencia, Spain
11Hematology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain
12Hospital Clinic Barcelona, Barcelona, Spain
13Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
14Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain
15Hematology Department, ICO Badalona, Germans Trias i Pujol University Hospital. Universitat Autònoma de Barcelona. Josep Carreras Leukemia Research Institute, Barcelona, Spain
16Hospital Duran i Reynals (Institut Català d'Oncologia), Hospitalet de Llobregat, Barcelona, Spain
17General University Hospital Gregorio Marañón, Madrid, Spain
18Hematology Department, Lyon Sud Hospital, Pierre-Bénite, France
19Oncology Data Science Group, Vall D'Hebron Institute of Oncology. Barcelona, Spa, Barcelona, Spain

Introduction: Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. There is no standard treatment after CAR T-cell therapy progression and a wide range of outcomes are observed in this patient population. Besides the interval between CAR T-cell infusion and progressive disease (PD), data regarding prognostic factors at time of progression are scarce. Our aim was to develop a new prognostic tool to predict overall survival (OS) after CAR T-cell therapy progression with easily-available markers from routine clinical practice.

Methods: First, we performed a retrospective data collection at 12 Spanish centers of R/R LBCL patients who progressed after CAR T-cell therapy in the third or later line setting from September 2018 until June 2022 (training cohort, TC). We analyzed a total of 15 variables, including pre-CAR T-cell therapy characteristics (gender, histology, primary refractory disease, previous hematopoietic transplant, number of previous lines) and values collected at time of progression to CAR T-cells (age, stage, extranodal sites, ECOG, hemoglobin, neutrophils, platelets, LDH, best response to CAR T-cells, time from CAR T-cell infusion to PD). The primary endpoint was OS from date of progression to CAR T-cell therapy. A stratified Cox model was used to estimate hazard ratios (HRs) using post-progression treatment as a stratification factor. We used LASSO regression with minimum lambda to identify which variables had the highest prognostic impact on OS. Additionally, the factors with a lower contribution were eliminated to create a parsimonious model. The C-statistic was used to evaluate its discrimination. We examined the performance of the International Prognostic Index (IPI) score and Revised IPI (R-IPI) in this setting. Finally, we tested the score in an external validation cohort (VC) which included a comparable patient population from 3 European countries.

Results: Among the 216 LBCL patients included in the TC, most were male (66%), had an ECOG of 1 (48%) and stage IV disease (71%) at time of CAR T-cell therapy progression. Median time from CAR T-cell infusion to PD was 2.5 months (95CI% 1.9-2.9) and median follow-up from progression was 15 months. Salvage treatment was classified into 3 subgroups, including immunotherapy or targeted agents (43%), chemotherapy or radiotherapy (20%) and palliative care (38%).

To build the prognostic score, a total of 5 variables were selected. Each marker received 1 point (given the similar HR [1.48-1.77]), if they met defined criteria: ECOG (>0), hemoglobin (<10 g/dL), LDH (>2 x upper normal limit), number of extranodal sites (>1) and time from CAR T-cell infusion to PD (<4 months). Patients with 0-1 points were classified as low risk, 2 points as intermediate-low risk, 3 points as intermediate-high risk and 4 or 5 points as high risk.

In the TC, the 4 risk groups showed statistically significant differences in OS (Figure 1). In the low-risk group (n=39 [18%]), the median OS [mOS] was not reached; in the intermediate-low risk (n=56 [26%]) mOS was 7.3 months (HR=2.89, p=0.002); in the intermediate-high risk (n=57 [26%]) mOS was 4.9 months (HR=4.81, p<0.001) and in the high risk (n=64 [30%]) mOS was 1.8 months (HR=6.69, p<0.001). In terms of post-relapse therapies, both the chemo/radiotherapy and the immunotherapy groups showed a balanced patient distribution, from low to high risk (32%, 35%, 14% and 19% vs 22%, 32%, 30% and 16%, respectively).

The VC included 204 patients with a similar patient distribution in the 4 prognostic risk groups (35%, 25%, 12%, 27%). The mOS for each of these groups was 15.2, 5.3, 2.9 and 0.9 months, respectively. Each group had distinct OS outcomes when compared with all the other risk groups (p<0.05 for each comparison) (Figure 2).

Finally, our model presented a C-index of 0.712 for the TC and 0.811 for the VC, outperforming both the IPI (0.647 [TC] and 0.691 [VC]) and R-IPI (0.632 [TC] and 0.683 [VC]).

Conclusions: The Post-CAR Prognostic Index (PC-PI) is a clinically useful tool for OS prediction and risk-adapted treatment planning in LBCL patients progressing after CAR T-cell therapy. In addition, our results will help stratification in clinical trials which include patients with prior CAR T-cell therapy.

Disclosures: Iacoboni: Autolus: Consultancy; Abbvie: Honoraria; Gilead Sciences: Consultancy, Honoraria; MSD: Honoraria; Novartis: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria; Janssen: Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; AstraZeneca: Honoraria. Sesques: KITE/GILEAD , BMS, JANSSEN, NOVARTIS, CHUGAI: Consultancy. Rejeski: Kite/Gilead: Other: Travel Support, Research Funding; Novartis: Honoraria; BMS/CELGENE: Consultancy, Honoraria; Pierre-Fabre: Other: Travel Support. Bastos-Oreiro: Kite-Gilead: Honoraria, Other: travel. Guerreiro: Novartis: Honoraria, Other: travel; Kite-Gilead: Honoraria, Other: travel; MSD: Honoraria, Other: TRAVEL; Pierre Fabre: Honoraria, Other: travel; BMS: Honoraria, Other: travel support. Martinez-Cibrian: Kite: Honoraria, Other: Travel support. Ghesquieres: Gilead, Roche: Consultancy; Gilead, Roche, BMS, Abbvie: Honoraria. Barba: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nektar: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pierre-Fabre: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lopez Corral: Janssen: Honoraria, Other: travel support; Novartis: Honoraria, Other: travel support; Gilead Sciences: Honoraria, Other: travel support. Reguera: AMGEN: Speakers Bureau; KITE: Speakers Bureau; BMS: Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Sureda Balari: MSD: Research Funding; Kite: Consultancy, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Martin Garcia-Sancho: Clinigen: Consultancy; Eusa Pharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead / Kite: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; ADC Therapeutics America: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria; Ideogen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd, BMS / Celgene, Kyowa Kirin, Novartis, Gilead / Kite, Incyte, Lilly, ADC Therapeutics America, Miltenyi, Ideogen, Abbvie, Sobi: Consultancy; F. Hoffmann-La Roche Ltd, BMS/Celgene, Janssen, Gilead/Kite, Takeda, Eusa Pharma, Abbvie: Honoraria; Kyowa Kirin: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Kwon: Jazz: Speakers Bureau; Pfizer: Speakers Bureau; Kite-Gilead: Consultancy, Speakers Bureau. Kuhnl: Novartis: Honoraria, Research Funding; Kite Gilead: Honoraria; BMS: Honoraria; Abbvie: Honoraria. Subklewe: Gilead/Kite: Consultancy, Honoraria, Other: Travel Support, Research Funding, Speakers Bureau; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seagen: Research Funding; Roche: Consultancy, Honoraria, Other: Travel Support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding; AstraZeneca: Speakers Bureau; Pfizer: Consultancy, Honoraria, Other: Travel Support, Speakers Bureau; Ichnos Sciences: Consultancy, Honoraria; AvenCell: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte Biosciences: Consultancy, Honoraria; Molecular Partners: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Speakers Bureau; LAWG: Speakers Bureau; Springer Healthcare: Speakers Bureau; AbbVie: Consultancy, Honoraria; Autolus: Consultancy, Honoraria; advesya (CanCell Therapeutics): Consultancy, Honoraria; Genmab US: Consultancy, Honoraria; Interius BioTherapeutics: Consultancy, Honoraria; Nektar Therapeutics: Consultancy, Honoraria; Orbital Therapeutics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Scare: Consultancy, Honoraria. Bachy: Takeda: Honoraria; Bristol Myers Squibb: Honoraria, Other: Personal Fees, Research Funding; Incyte: Honoraria; Novartis: Honoraria, Other: Personal Fees; Pfizer: Honoraria, Other: Personal Fees; Hospices Civils de Lyon Claude Bernard Lyon 1 University: Current Employment; Amgen: Research Funding; Roche: Consultancy, Honoraria; Kite, a Gilead Company: Honoraria, Other: Personal Fees.

*signifies non-member of ASH