Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan.
Algorithm
CAR-T
Lymphoma
Metabolic tumor volume
Tisagenlecleucel
Journal
International journal of clinical oncology
ISSN: 1437-7772
Titre abrégé: Int J Clin Oncol
Pays: Japan
ID NLM: 9616295
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
21
12
2022
accepted:
28
03
2023
medline:
2
6
2023
pubmed:
19
4
2023
entrez:
18
4
2023
Statut:
ppublish
Résumé
Tisagenlecleucel, an autologous CD19-directed T-cell immunotherapy, can induce a durable response in adult patients with relapsed/refractory (r/r) B-cell lymphoma. To elucidate the outcome of chimeric antigen receptor (CAR) T-cell therapy in Japanese, we retrospectively analyzed the outcomes of 89 patients who received tisagenlecleucel for r/r diffuse large B-cell lymphoma (n = 71) or transformed follicular lymphoma (n = 18). With a median follow-up of 6.6-months, 65 (73.0%) patients achieved a clinical response. The overall survival (OS) and event-free survival (EFS) rates at 12 months were 67.0% and 46.3%, respectively. Overall, 80 patients (89.9%) had cytokine release syndrome (CRS), and 6 patients (6.7%) had a grade ≥ 3 event. ICANS occurred in 5 patients (5.6%); only 1 patient had grade 4 ICANS. Representative infectious events of any grade were cytomegalovirus viremia, bacteremia and sepsis. The most common other adverse events were ALT elevation, AST elevation, diarrhea, edema, and creatinine elevation. No treatment-related mortality was observed. A Sub-analysis showed that a high metabolic tumor volume (MTV; ≥ 80 ml) and stable disease /progressive disease before tisagenlecleucel infusion were both significantly associated with a poor EFS and OS in a multivariate analysis (P < 0.05). Notably, the combination of these 2 factors efficiently stratified the prognosis of these patients (HR 6.87 [95% CI 2.4-19.65; P < 0.05] into a high-risk group). We report the first real-world data on tisagenlecleucel for r/r B-cell lymphoma in Japan. Tisagenlecleucel is feasible and effective, even in late line treatment. In addition, our results support a new algorithm for predicting the outcomes of tisagenlecleucel.
Sections du résumé
BACKGROUND
BACKGROUND
Tisagenlecleucel, an autologous CD19-directed T-cell immunotherapy, can induce a durable response in adult patients with relapsed/refractory (r/r) B-cell lymphoma.
METHODS
METHODS
To elucidate the outcome of chimeric antigen receptor (CAR) T-cell therapy in Japanese, we retrospectively analyzed the outcomes of 89 patients who received tisagenlecleucel for r/r diffuse large B-cell lymphoma (n = 71) or transformed follicular lymphoma (n = 18).
RESULTS
RESULTS
With a median follow-up of 6.6-months, 65 (73.0%) patients achieved a clinical response. The overall survival (OS) and event-free survival (EFS) rates at 12 months were 67.0% and 46.3%, respectively. Overall, 80 patients (89.9%) had cytokine release syndrome (CRS), and 6 patients (6.7%) had a grade ≥ 3 event. ICANS occurred in 5 patients (5.6%); only 1 patient had grade 4 ICANS. Representative infectious events of any grade were cytomegalovirus viremia, bacteremia and sepsis. The most common other adverse events were ALT elevation, AST elevation, diarrhea, edema, and creatinine elevation. No treatment-related mortality was observed. A Sub-analysis showed that a high metabolic tumor volume (MTV; ≥ 80 ml) and stable disease /progressive disease before tisagenlecleucel infusion were both significantly associated with a poor EFS and OS in a multivariate analysis (P < 0.05). Notably, the combination of these 2 factors efficiently stratified the prognosis of these patients (HR 6.87 [95% CI 2.4-19.65; P < 0.05] into a high-risk group).
CONCLUSION
CONCLUSIONS
We report the first real-world data on tisagenlecleucel for r/r B-cell lymphoma in Japan. Tisagenlecleucel is feasible and effective, even in late line treatment. In addition, our results support a new algorithm for predicting the outcomes of tisagenlecleucel.
Identifiants
pubmed: 37071252
doi: 10.1007/s10147-023-02334-w
pii: 10.1007/s10147-023-02334-w
doi:
Substances chimiques
tisagenlecleucel
Q6C9WHR03O
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
816-826Informations de copyright
© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.
Références
Sehn LH, Gascoyne RD (2015) Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood 125(1):22–32
doi: 10.1182/blood-2014-05-577189
pubmed: 25499448
Tilly H, Morschhauser F, Sehn LH et al (2022) Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med 386(4):351–363
doi: 10.1056/NEJMoa2115304
pubmed: 34904799
Crump M, Neelapu SS, Farooq U et al (2017) Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 130(16):1800–1808
doi: 10.1182/blood-2017-03-769620
pubmed: 28774879
pmcid: 5649550
Van Den Neste E, Schmitz N, Mounier N et al (2016) Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant 51(1):51–57
doi: 10.1038/bmt.2015.213
pubmed: 26367239
Schuster SJ, Tam CS, Borchmann P et al (2021) 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 22(10):1403–1415
doi: 10.1016/S1470-2045(21)00375-2
pubmed: 34516954
Pasquini MC, Hu ZH, Curran K et al (2020) Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Adv 4(21):5414–5424
doi: 10.1182/bloodadvances.2020003092
pubmed: 33147337
pmcid: 7656920
Goto H, Makita S, Kato K et al (2020) Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma. Int J Clin Oncol 25(9):1736–1743
doi: 10.1007/s10147-020-01699-6
pubmed: 32448949
pmcid: 7441082
Schuster SJ, Bishop MR, Tam CS et al (2019) Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 380(1):45–56
doi: 10.1056/NEJMoa1804980
pubmed: 30501490
Vercellino L, Di Blasi R, Kanoun S et al (2020) Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv 4(22):5607–5615
doi: 10.1182/bloodadvances.2020003001
pubmed: 33180899
pmcid: 7686887
Cheson BD, Fisher RI, Barrington SF et al (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32(27):3059–3068
doi: 10.1200/JCO.2013.54.8800
pubmed: 25113753
pmcid: 4979083
Jain T, Bar M, Kansagra AJ et al (2019) Use of chimeric antigen receptor T cell therapy in clinical practice for relapsed/refractory aggressive b cell non-Hodgkin lymphoma: an expert panel opinion from the american society for transplantation and cellular therapy. Biol Blood Marrow Transplant 25(12):2305–2321
doi: 10.1016/j.bbmt.2019.08.015
pubmed: 31446199
Senjo H, Hirata K, Izumiyama K et al (2020) High metabolic heterogeneity on baseline 18FDG-PET/CT scan as a poor prognostic factor for newly diagnosed diffuse large B-cell lymphoma. Blood Adv 4(10):2286–2296
doi: 10.1182/bloodadvances.2020001816
pubmed: 32453838
pmcid: 7252551
Hirata K, Kobayashi K, Wong KP et al (2014) A semi-automated technique determining the liver standardized uptake value reference for tumor delineation in FDG PET-CT. PLoS ONE 9(8):e105682
doi: 10.1371/journal.pone.0105682
pubmed: 25162396
pmcid: 4146536
Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48(3):452–458
doi: 10.1038/bmt.2012.244
pubmed: 23208313
Hirayama AV, Gauthier J, Hay KA et al (2019) The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood 133(17):1876–1887
doi: 10.1182/blood-2018-11-887067
pubmed: 30782611
pmcid: 6484391
Hay KA, Gauthier J, Hirayama AV et al (2019) Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy. Blood 133(15):1652–1663
doi: 10.1182/blood-2018-11-883710
pubmed: 30728140
pmcid: 6460418
Sarris AH, Majlis A, Dimopoulos MA et al (1995) Rising serum lactate dehydrogenase often caused by granulocyte-or Granulocyte-macrophage colony stimulating factor and not tumor progression in patients with lymphoma or myeloma. Leuk Lymphoma 17(5–6):473–477
doi: 10.3109/10428199509056860
pubmed: 7549840
Bakker J, de Backer D, Hernandez G (2016) Lactate-guided resuscitation saves lives: we are not sure. Intensive Care Med 42(3):472–474
doi: 10.1007/s00134-016-4220-z
pubmed: 26831675
Tabbara IA (1992) Hemolytic anemias. Diagnosis and management. Med Clin North Am 76(3):649–668
doi: 10.1016/S0025-7125(16)30345-5
pubmed: 1578962
Hong R, Yin TS, E, Wang L, et al (2021) Tumor burden measured by 18F-FDG PET/CT in predicting efficacy and adverse effects of chimeric antigen receptor T-Cell therapy in non-Hodgkin lymphoma. Front Oncol 11:713577
doi: 10.3389/fonc.2021.713577
pubmed: 34422666
pmcid: 8371710
Lee DW, Santomasso BD, Locke FL et al (2019) ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 25(4):625–638
doi: 10.1016/j.bbmt.2018.12.758
pubmed: 30592986
Arcangeli S, Bove C, Mezzanotte C et al (2022) CAR T cell manufacturing from naive/stem memory T lymphocytes enhances antitumor responses while curtailing cytokine release syndrome. J Clin Invest 132(12):e150807
doi: 10.1172/JCI150807
pubmed: 35503659
pmcid: 9197529
Giavridis T, van der Stegen SJC, Eyquem J et al (2018) CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med 24(6):731–738
doi: 10.1038/s41591-018-0041-7
pubmed: 29808005
pmcid: 6410714
Xiao X, Huang S, Chen S et al (2021) Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies. J Exp Clin Cancer Res 40(1):367
doi: 10.1186/s13046-021-02148-6
pubmed: 34794490
pmcid: 8600921