Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment.
CAR-T
Disease progression
Large B-cell lymphoma
Overall survival
Score
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
22
07
2024
accepted:
15
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to PD (< 4 months). Patients were classified in four risk groups with distinct OS (p-value < 0.05 in all comparisons). In the validation cohort, median OS in the low (31%), intermediate-low (26%), intermediate-high (17%) and high risk (26%) were 15.7, 7.1, 1.8 and 1.0 months, respectively (p < 0.05 in all comparisons). Results were consistent following adjustment for subsequent treatment. In the external cohort, the PC-PI showed a C-statistic of 0.79 (95%CI 0.76-0.82), outperforming IPI and R-IPI. In conclusion, the PC-PI score is a novel tool for OS prediction and could facilitate risk-adapted management of LBCL patients relapsing after CAR T-cells. Additionally, these results will help stratification and interpretation of trials and real-world data incorporating CART-exposed patients.
Identifiants
pubmed: 39468591
doi: 10.1186/s13045-024-01608-8
pii: 10.1186/s13045-024-01608-8
doi:
Types de publication
Validation Study
Letter
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102Informations de copyright
© 2024. The Author(s).
Références
Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO et al. 5-Year Follow-Up supports curative potential of Axicabtagene Ciloleucel in Refractory large B-Cell lymphoma (ZUMA-1). Blood. 2023.
Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(10):1403–15.
doi: 10.1016/S1470-2045(21)00375-2
pubmed: 34516954
Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, et al. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024;143(5):404–16.
doi: 10.1182/blood.2023020854
pubmed: 37890149
Pasquini MC, Hu ZH, Curran K, Laetsch T, Locke F, Rouce R, et al. Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-hodgkin lymphoma. Blood Adv. 2020;4(21):5414–24.
doi: 10.1182/bloodadvances.2020003092
pubmed: 33147337
pmcid: 7656920
Iacoboni G, Villacampa G, Martinez-Cibrian N, Bailén R, Lopez Corral L, Sanchez JM, et al. Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Cancer Med. 2021;10(10):3214–23.
doi: 10.1002/cam4.3881
pubmed: 33932100
pmcid: 8124109
Jacobson CA, Locke FL, Ma L, Asubonteng J, Hu ZH, Siddiqi T, et al. Real-world evidence of Axicabtagene Ciloleucel for the treatment of large B cell lymphoma in the United States. Transpl Cell Ther. 2022;28(9):581.e1-.e8.
Kwon M, Iacoboni G, Reguera JL, Corral LL, Morales RH, Ortiz-Maldonado V et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. Haematologica. 2022.
Bachy E, Le Gouill S, Di Blasi R, Sesques P, Manson G, Cartron G, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28(10):2145–54.
doi: 10.1038/s41591-022-01969-y
pubmed: 36138152
pmcid: 9556323
Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, et al. GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140(4):349–58.
pubmed: 35316325
Kuhnl A, Roddie C, Kirkwood AA, Tholouli E, Menne T, Patel A, et al. A national service for delivering CD19 CAR-Tin large B-cell lymphoma - the UK real-world experience. Br J Haematol. 2022;198(3):492–502.
doi: 10.1111/bjh.18209
pubmed: 35485402
Di Blasi R, Le Gouill S, Bachy E, Cartron G, Beauvais D, Le Bras F et al. Outcomes of patients with aggressive B-Cell lymphoma after failure of anti-CD19 CAR T-Cell therapy: a DESCAR-T analysis. Blood. 2022.
Zurko JC, Nizamuddin I, Epperla N, David KA, Cohen JB, Moyo T et al. Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL. Blood Adv. 2022.
Alarcon Tomas A, Fein JA, Fried S, Flynn JR, Devlin SM, Fingrut WB et al. Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma. Leukemia. 2022.
Iacoboni G, Iraola-Truchuelo J, O’Reilly M, Navarro V, Menne T, Kwon M, et al. Treatment outcomes in patients with large B-cell lymphoma after progression to chimeric antigen receptor T-cell therapy. Hemasphere. 2024;8(5):e62.
doi: 10.1002/hem3.62
pubmed: 38774657
pmcid: 11106798
Nastoupil LJ, Jain MD, Feng L, Spiegel JY, Ghobadi A, Lin Y, et al. Standard-of-care Axicabtagene Ciloleucel for relapsed or refractory large B-Cell lymphoma: results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2020;38(27):3119–28.
doi: 10.1200/JCO.19.02104
pubmed: 32401634
pmcid: 7499611
Jacobson CA, Hunter BD, Redd R, Rodig SJ, Chen PH, Wright K, et al. Axicabtagene Ciloleucel in the Non-trial setting: outcomes and correlates of response, resistance, and toxicity. J Clin Oncol. 2020;38(27):3095–106.
doi: 10.1200/JCO.19.02103
pubmed: 32667831
pmcid: 7499617
Garcia-Recio M, Wudhikarn K, Pennisi M, Alonso-Trillo R, Flynn J, Shouval R, et al. The International Prognostic Index is Associated with outcomes in diffuse large B cell lymphoma after Chimeric Antigen Receptor T Cell Therapy. Transpl Cell Ther. 2021;27(3):233–40.
doi: 10.1016/j.jtct.2020.10.022
Rejeski K, Perez A, Iacoboni G, Penack O, Bücklein V, Jentzsch L et al. The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL. J Immunother Cancer. 2022;10(5).
Project IN-HLPF. A predictive model for aggressive non-hodgkin’s lymphoma. N Engl J Med. 1993;329(14):987–94.
doi: 10.1056/NEJM199309303291402
Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–61.
doi: 10.1182/blood-2006-08-038257
pubmed: 17105812
Westin JR, Oluwole OO, Kersten MJ, Miklos DB, Perales MA, Ghobadi A, et al. Survival with Axicabtagene Ciloleucel in large B-Cell lymphoma. N Engl J Med. 2023;389(2):148–57.
doi: 10.1056/NEJMoa2301665
pubmed: 37272527
Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene Ciloleucel as Second-Line therapy for large B-Cell lymphoma. N Engl J Med. 2022;386(7):640–54.
doi: 10.1056/NEJMoa2116133
pubmed: 34891224
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294–308.
doi: 10.1016/S0140-6736(22)00662-6
pubmed: 35717989
Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022;28(4):735–42.
doi: 10.1038/s41591-022-01731-4
pubmed: 35314842
pmcid: 9018426
https:// www.clinicaltrials.gov/study/NCT03960840?cond=NCT03960840&rank=1#study-plan
Westin J, Jacobson CA, Chavez JC, Sureda A, Morschhauser F, Glaß B, CONTROLLED STUDY OF AXICABTAGENE CILOLEUCEL VERSUS STANDARD OF CARE AS FIRST-LINE THERAPY IN PATIENTS WITH HIGH-RISK LARGE B-CELL LYMPHOMA. ZUMA-23: A GLOBAL, PHASE 3, RANDOMIZED. Hematol Oncol. 2023;41(S2):171–3.
doi: 10.1002/hon.3163_T06
Maurer MJ, Jakobsen LH, Mwangi R, Schmitz N, Farooq U, Flowers CR, et al. Relapsed/Refractory International Prognostic Index (R/R-IPI): an international prognostic calculator for relapsed/refractory diffuse large B-cell lymphoma. Am J Hematol. 2021;96(5):599–605.
doi: 10.1002/ajh.26149
pubmed: 33661547
pmcid: 8763015
Buecklein VL, Rejeski K, Perez A, Iacoboni G, Jurinovic V, Kharboutli S, et al. Impact of sex on clinical outcomes after CD19 CAR T-Cell therapy for large B-Cell lymphoma: response and survival are significantly Superior in Female compared to male patients. Blood. 2023;142(Supplement 1):3787.
doi: 10.1182/blood-2023-186510
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86.
doi: 10.1200/JCO.2006.09.2403
pubmed: 17242396
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68.
doi: 10.1200/JCO.2013.54.8800
pubmed: 25113753
pmcid: 4979083
Lausen B, Schumacher M. Maximally selected Rank statistics. Biometrics. 1992;48(1):73–85.
doi: 10.2307/2532740
https:// cran.r-project.org/web/packages/survminer/index.html
Kang L, Chen W, Petrick NA, Gallas BD. Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach. Stat Med. 2015;34(4):685–703.
doi: 10.1002/sim.6370
pubmed: 25399736
https:// cran.r-project.org/web/packages/compareC/index.html
Harrell FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361–87.
doi: 10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4
pubmed: 8668867
van Buuren S, Groothuis-Oudshoorn K. Mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1–67.
doi: 10.18637/jss.v045.i03
Wolff RF, Moons KGM, Riley RD, Whiting PF, Westwood M, Collins GS, et al. PROBAST: A Tool to assess the risk of Bias and Applicability of Prediction Model studies. Ann Intern Med. 2019;170(1):51–8.
doi: 10.7326/M18-1376
pubmed: 30596875
TRIPOD. www.tripod-statement.org.
Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, et al. Follicular lymphoma international prognostic index. Blood. 2004;104(5):1258–65.
doi: 10.1182/blood-2003-12-4434
pubmed: 15126323
Berning P, Shumilov E, Maulhardt M, Boyadzhiev H, Kerkhoff A, Call S, et al. Chimeric antigen receptor-T cell therapy shows similar efficacy and toxicity in patients with diffuse large B-cell lymphoma aged 70 and older compared to younger patients: a multicenter cohort study. Hemasphere. 2024;8(3):e54.
doi: 10.1002/hem3.54
pubmed: 38510993
pmcid: 10953542
Ram R, Grisariu S, Shargian-Alon L, Amit O, Bar-On Y, Stepensky P, et al. Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients - a matched control multicenter cohort study. Haematologica. 2022;107(5):1111–8.
doi: 10.3324/haematol.2021.278288
pubmed: 34233446
Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, et al. CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138(24):2499–513.
doi: 10.1182/blood.2020010543
pubmed: 34166502
pmcid: 8893508
Rejeski K, Perez A, Iacoboni G, Blumenberg V, Bücklein VL, Völkl S, et al. Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion. Sci Adv. 2023;9(38):eadg3919.
doi: 10.1126/sciadv.adg3919
pubmed: 37738350
pmcid: 10516499
Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141(14):1675–84.
doi: 10.1182/blood.2022018730
pubmed: 36542826