Abstract
Identification of Pre-Treatment Clinical Risk Factors Predictive of Inferior Survival and Increased Risk of Treatment Failure in CD19 Chimeric Antigen Receptor T Cell Recipients with Large B Cell Lymphoma
Transplantation and cellular therapy, Vol.30(2 Supplement), pp.S358-S359
02/2024
DOI: 10.1016/j.jtct.2023.12.501
Abstract
CD19 chimeric antigen receptor T-cells (CAR T) elicit remarkable anti-lymphoma activity offering an excellent response rate and durable disease control. Yet, patients have variable responses. This study analyzes factors associated with therapeutic efficacy in a large real-world patient cohort treated with commercial CAR T-cells for relapse/refractory large B-cell lymphoma (R/R LBCL).
This was an observational study of adult recipients of commercial CAR T-cells for treatment of R/R LBCL between May 2018 and July 2020 from the CIBMTR registry. Response rate, progression-free (PFS) and overall survival (OS) were the primary outcomes. Multivariable analysis was performed and adjusted using Cox proportional hazards models to determine factors associated with favorable response and survival outcomes.
1916 patients with R/R LBCL received commercial CD19 CAR T-cell products (1435 axicabtagene ciloleucel and 481 tisagenlecleucel) (Figure 1). The median age was 63 years (range 18-91). A total of 461 patients (24%) had transformed LBCL. Approximately 64% of patients received ≥3 prior lines of treatment including 496 patients with prior autologous hematopoietic cell transplantation (HCT) (192; 39% relapsed within 12 months from HCT). The median time from first diagnosis of de-novo or transformed LBCL to CAR T cell therapy was 14.7 months (range 0.8-406) with 640 patients (33%) receiving bridging therapy prior to CAR T-cell infusion. The best overall response rate (ORR) at 1 year was 75% including 65% complete responses (CR) and 10% partial responses (PR). At a median follow up time of 14 months, 843 patients (44%) had died. The estimated 1-year PFS and OS was 42% and 62%, respectively. The major cause of death was disease progression as reported in 618 patients (75%) with the 1-year relapse incidence of 55%. Multivariable analysis demonstrated age ≥ 65 years, female gender, normal lactate dehydrogenase (LDH) prior to CAR T, receipt of axicabtagene ciloleucel, and absence of comorbidities as predictors for achieving CR after CAR T-cell. Risk factors for treatment failure (inferior PFS) included male gender, poor performance status (<80 Karnofsky score), elevated LDH, early relapse within 12 months following HCT, resistant disease prior to CAR T-cell, receipt of tisagenlecleucel and presence of comorbidities (Figure 2). Predictors of poor OS included poor performance status, elevated LDH, early relapse post-HCT, resistant disease at the time of CAR T-cell and presence of comorbidities.
Several clinical patient, disease and CAR T-cell product related factors were associated with better response and survival in patients with R/R LBCL following CD19 CAR T-cell therapy. This study helps identify patients at risk of treatment failure who may benefit from mitigation strategies pre- and post-CAR T to maximize efficacy of CAR T-cell therapy.
Details
- Title: Subtitle
- Identification of Pre-Treatment Clinical Risk Factors Predictive of Inferior Survival and Increased Risk of Treatment Failure in CD19 Chimeric Antigen Receptor T Cell Recipients with Large B Cell Lymphoma
- Creators
- Praveen Ramakrishnan Geethakumari - The University of Texas Southwestern Medical CenterKitsada Wudhikarn - Chulalongkorn UniversityChristopher Sun Strouse - University of IowaMichael D. Jain - Moffitt Cancer CenterAnusha Vallurupalli - Oregon Health & Science UniversitySoyoung Kim - Medical College of WisconsinTemitope Oloyede - Medical College of WisconsinFarrukh T Awan - The University of Texas Southwestern Medical CenterAbu-Sayeef Mirza - Yale UniversityVeronika Bachanova - University of Minnesota Medical CenterTalha Badar - Mayo Clinic in FloridaPere Barba - Universitat Autònoma de BarcelonaAmer Beitinjaneh - Sylvester Comprehensive Cancer CenterAmanda Cashen - Washington University in St. LouisBhagirathbhai Dholaria - Vanderbilt University Medical CenterMahmoud Elsawy - Dalhousie UniversityUmar Farooq - University of IowaJessica Foglesong - Lurie Children's HospitalSiddhartha Ganguly - Houston MethodistUri Greenbaum - Soroka Medical CenterHamza Hashmi - Medical University of South CarolinaLaQuisa Chimere Hill - Baylor College of MedicineDr. Tania Jain - Johns Hopkins UniversityPartow Kebriaei - The University of Texas MD Anderson Cancer CenterAdam S. Kittai - The Ohio State UniversityFrederick L. Locke - Moffitt Cancer CenterPremal D. Lulla - Baylor College of MedicineElena Mead - Memorial Sloan Kettering Cancer CenterJoseph P McGuirk - The University of Kansas Cancer CenterAlberto Mussetti - Institut Català d'OncologiaTaiga Nishihori - Moffitt Cancer CenterAmanda L. Olson - The University of Texas MD Anderson Cancer CenterMartina Pennisi - Memorial Sloan Kettering Cancer CenterMiguel-Angel Perales - Memorial Sloan Kettering Cancer CenterPeter A. Riedell - University of ChicagoWael Saber - Medical College of WisconsinRoni Shouval - University of Minnesota Medical CenterElizabeth J. Shpall - The University of Texas MD Anderson Cancer CenterMohamed L. Sorror - University of WashingtonCameron J. Turtle - University of WashingtonMarcelo C. Pasquini - Medical College of WisconsinAmy Moskop - Medical College of WisconsinSairah Ahmed - The University of Texas MD Anderson Cancer Center
- Resource Type
- Abstract
- Publication Details
- Transplantation and cellular therapy, Vol.30(2 Supplement), pp.S358-S359
- DOI
- 10.1016/j.jtct.2023.12.501
- ISSN
- 2666-6367
- eISSN
- 2666-6367
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984559773602771
Metrics
9 Record Views