Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti-CD19-chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B-cell lymphoma and high tumor burden.
chimeric antigen receptor (CAR)
diffuse large B-cell lymphoma
maintenance therapy
programmed cell death 1 inhibitors
relapsed/refractory
tumor burden
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
17
02
2022
received:
25
11
2021
accepted:
19
02
2022
medline:
10
4
2023
pubmed:
24
2
2022
entrez:
23
2
2022
Statut:
ppublish
Résumé
We studied the efficacy and safety of the combined treatment with programmed cell death 1 (PD-1) inhibitors and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and subsequent PD-1 inhibitor maintenance treatment in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and high tumor burden. Forty-four R/R DLBCL patients with high tumor burden were enrolled in this study. The experimental group of 26 patients received combined therapy with PD-1 inhibitors and anti-CD19-CAR T cells, while the control group of 18 patients received anti-CD19-CAR T-cell therapy alone. The objective response rate (ORR) was 65.39% and 61.11% in the combination and control groups, respectively. The PD-1 inhibitor maintenance therapy was selected for patients who achieved complete response or partial response in the combination therapy group. Progression-free survival and overall survival rates in the combination group were higher than those in the control group 3 and 12 months after CAR T-cell infusion. There was no significant difference in the grade of cytokine release syndrome or immune effector cell associated neurotoxic syndrome between the two groups. In the maintenance therapy group, only eight patients experienced grade 1 Common Terminology Criteria for Adverse Events (CTCAE) and three grade 2 CTCAE. Overall, we found that the ORR was not affected by the combination therapy with PD-1 inhibitors and anti-CD19-CAR T cells. However, patients who had achieved the ORR might benefit from PD-1 inhibitor maintenance therapy after combination therapy without increased side effects.
Substances chimiques
Receptors, Chimeric Antigen
0
Immune Checkpoint Inhibitors
0
Antigens, CD19
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
275-284Subventions
Organisme : The National Natural Science Foundation of China
ID : (81900186)
Organisme : Key R & D projects of Ningxia Hui Autonomous Region
ID : 2021BEG03036
Organisme : Key R & D projects of Ningxia Hui Autonomous Region
ID : 2021BEG03036
Organisme : National Natural Science Foundation of China
ID : 81900186
Informations de copyright
© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
Références
Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Eng J Med. 2002;346:235-242.
Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116:2040-2045.
Chow VA, Shadman M, Gopal AK. Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. Blood. 2018;132(8):777-781.
Neelapu SS, Locke FL, Bartlett NL, et al. AxicabtageneCiloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544.
Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56.
Vercellino L, Di Blasi R, Kanoun S, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020;4:5607-5615.
Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associatedwith poor prognosis in patients with diffuse large B-cell lymphomatreated in the era of rituximab. J Clin Oncol. 2010;28:3360-3365.
Savage KJ, Johnson NA, Ben-Neriah S, et al. MYC gene rearrangementsare associated with a poor prognosis in diffuse largeB-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009;114:3533-3537.
Xu-Monette ZY, Deng Q, Manyam GC, et al. Clinical andbiologic significance of MYC genetic mutations in de novo diffuselarge B-cell lymphoma. Clin Cancer Res. 2016;22:3593-3605.
Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Immunol. 2005;23:515-548.
Elhelbawy NG, Nassar AAH, Eltorgoman AEA, Saber SM, Badr EA. Immunological microenvironment gene expression in patients with diffuse large B cell non Hodgkin lymphoma. BiochemBiophys Rep. 2020;21:100731.
Cohen M, Vistarop AG, Huaman F, et al. Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: clinical features and survival impact. Sci Rep. 2017;7(1):10813.
Li S, Siriwon N, Zhang X, et al. Enhanced cancer immunotherapy by chimeric antigen receptor-modified T cells engineered to secrete checkpoint inhibitors. Clin Cancer Res. 2017;23(22):6982-6992.
Robinson SP, Boumendil A, Finel H, et al. Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants, A report from the EBMT Lymphoma Working Party. Bone Marrow Transpl. 2016;51(3):365-371.
Landsburg DJ, Koike A, Nasta SD, et al. Patterns of immune checkpoint protein expression in MYC-overexpressing aggressive B-cell non-Hodgkin lymphomas. Cancer Immunol Immunother. 2021;70:869-874.
Läubli H, Balmelli C, Bossard M, Pfister O, Glatz K, Zippelius A. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015;3:11.
Cheson BD, Fisher RI, Barrington SF, et al. Southwest oncology group; United Kingdom national cancer research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-hodgkin lymphoma: the lugano classification. J Clin Oncol. 2014;32(27):3059-3067.
Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195.
Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for CytokineRelease syndrome and neurologic toxicity associated with immune effector cells. Biology ofblood and marrow transplantation. J Am Soc Blood MarrowTransplantation. 2019;25(4):625-638.
Common NIH. Terminology Criteria for Adverse Events (CTCAE). 2017 https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf
Kochenderfer JN, Dudley ME, Kassim SH, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540-549.
Yan ZX, Li L, Wang W, et al. Clinical efficacy and tumor microenvironment influence in a dose-escalation study of anti-CD19 chimeric antigen receptor T cells in refractory B-cell non-hodgkin's lymphoma. Clin Cancer Res. 2019;25(23):6995-7003.
Guedan S, Ruella M, June CH. Emerging cellular therapies for cancer. Annu Rev Immunol. 2019;37:145-171.
Qu C, Ping N, Kang L, et al. Radiation priming chimeric antigen receptor T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma with high tumor burden. J Immunother. 2020;43(1):32-37.
Pedoeem A, Azoulay-Alfaguter I, Strazza M, Silverman GJ, Mor A. Programmed death-1 pathway in cancer and autoimmunity. Clin Immunol. 2014;153(1):145-152.
Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568-571.
Wang C, Yu J, Fan Y, et al. The clinical significance of PD-L1/PD-1 expression in gastroenteropancreatic neuroendocrine neoplasia. Ann Clin Lab Sci. 2019;49(4):448-456.
Majzner RG, Mackall CL. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med. 2019;25(9):1341-1355.
Schuster SJ, Svoboda J, Chong EA, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377(26):2545-2554.
Lipson EJ, Sharfman WH, Drake CG, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res. 2013;19(2):462-468.
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454.
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372(4):311-319.
Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31(33):4199-4206.
Zhang R, Lyu C, Lu W, Pu Y, Jiang Y, Deng Q. Synergistic effect of programmed death-1 inhibitor and programmed death-1 ligand-1 inhibitor combined with chemotherapeutic drugs on DLBCL cell lines in vitro and in vivo. Am J Cancer Res. 2020;10(9):2800-2812.
Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers and combinations. Sci Transl Med. 2016;8(328):328rv4.