Online first
Case report
Published online: 2024-10-03
CAR-T cell therapy in evolving therapeutic landscape of relapsed or refractory primary mediastinal b-cell lymphoma (PMBCL): challenges and aspirations — two case reports
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DOI: 10.5603/hicp.98832
Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy is a promising option in patients with r/r PMBCL as a radical approach or a part of combined modality treatment. However, failure after CAR-T poses challenges to clinicians. The report presents two cases of patients with r/r PMBCL who received CAR-T therapy following several lines of chemotherapy. The first patient remains in complete metabolic remission 20 months after CAR-T infusion. The second case depicts the use of CAR-T in a combined treatment with bridging therapy to allogeneic haematopoietic stem cell transplantation (allo-HSCT). Combining radiotherapy with pembrolizumab remains a promising salvage therapy in patients who progressed or relapsed after CAR-T. Allo-HSCT is considered a viable consolidation strategy for young and fit patients with r/r disease who respond to bridging therapy. The ideal combination of CAR-T with novel agents and allo-HSCT is still developing and needs to be explored in prospective randomized trials.
Keywords: R/R PMBCLCAR-Taxi-celallo-HSCTsalvage therapy in R/R PMBCL
References
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20): 2375–2390.
- Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013; 368(15): 1408–1416.
- Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995; 333(23): 1540–1545.
- Lazzarino M, Orlandi E, Paulli M, et al. Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients. J Clin Oncol. 1997; 15(4): 1646–1653.
- Giulino-Roth L. How I treat primary mediastinal B-cell lymphoma. Blood. 2018; 132(8): 782–790.
- Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019; 37(34): 3291–3299.
- Morschhauser F, Dahiya S, Palomba ML, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396(10254): 839–852.
- Zinzani P, Ribrag V, Moskowitz C, et al. Phase 1b study of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma: results from the ongoing Keynote-013 trial. Blood. 2016; 128(22): 619–619.
- Chong EA, Ruella M, Schuster SJ, et al. Lymphoma Program Investigators at the University of Pennsylvania. Five-year outcomes for refractory B-cell lymphomas with CAR T-cell therapy. N Engl J Med. 2021; 384(7): 673–674.
- Varma G, Goldstein J, Advani RH. Novel agents in relapsed/refractory diffuse large B-cell lymphoma. Hematol Oncol. 2023; 41 Suppl 1: 92–106.
- Le Calvez B, Tessoullin B, Renaud L, et al. Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study. Acta Oncol. 2022; 61(11): 1332–1338.
- Zinzani PL, Santoro A, Gritti G, et al. Nivolumab combined with brentuximab vedotin for relapsed/refractory primary mediastinal large B-cell lymphoma: efficacy and safety from the phase II checkmate 436 study. J Clin Oncol. 2019; 37(33): 3081–3089.
- Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019; 37(34): 3291–3299.
- Cheson BD, Fisher RI, Barrington SF, et al. Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, 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): 3059–3068.
- Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019; 25(4): 625–638.
- Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the mount sinai acute GVHD international consortium. Biol Blood Marrow Transplant. 2016; 22(1): 4–10.
- Chiappella A, Dodero A, Guidetti A, et al. S231: primary mediastinal B-cell lymphoma have a superior outcome compared to diffuse large-B-cell lymphoma treated with axicabtagene ciloleucel in the CART-SIE real life Italian study. HemaSphere. 2023; 7(S3).
- Di Blasi R, Le Gouill S, Bachy E, 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; 140(24): 2584–2593.
- Caballero AC, Escribà-Garcia L, Alvarez-Fernández C, et al. CAR T-cell therapy predictive response markers in diffuse large B-cell lymphoma and therapeutic options after CART19 failure. Front Immunol. 2022; 13: 904497.
- Bastos-Oreiro M, Gutierrez A, Reguera JL, et al. Best treatment option for patients with refractory aggressive B-cell lymphoma in the CAR-T cell era: real-world evidence from GELTAMO/GETH spanish groups. Front Immunol. 2022; 13: 855730.
- Chen H, Pan T, He Y, et al. Primary mediastinal B-cell lymphoma: novel precision therapies and future directions. Front Oncol. 2021; 11: 654854.
- Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019; 16(6): 372–385.
- Jackson MW, Rusthoven CG, Jones BL, et al. Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma. Am J Hematol. 2016; 91(5): 476–480.
- Perrone S, Lopedote P, De Sanctis V, et al. Novel drugs and radiotherapy in relapsed lymphomas: abscopal response and beyond. Cancers (Basel). 2023; 15(10).
- Quéro L, Gilardin L, Fumagalli I, et al. Anti-PD-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma. Cancer Radiother. 2019; 23(2): 132–137.
- Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019; 37(34): 3291–3299.
- Prochazka V, Papajik T, Flodr P, et al. Programmed death-1 ligand is uniformly expressed on primary mediastinal diffuse large B-cell lymphoma cells with no influence on patient survival. Blood. 2012; 120(21): 2671–2671.
- Zinzani PL, Thieblemont C, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019; 37(34): 3291–3299.
- Cherkassky L, Morello A, Villena-Vargas J, et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016; 126(8): 3130–3144.
- Chong EA, Melenhorst JJ, Lacey SF, et al. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood. 2017; 129(8): 1039–1041.
- Fenske T, Ahn K, Graff T, et al. Allogeneic transplantation provides durable remission in a subset of
DLBCL patients relapsing after autologous transplantation. British Journal of Haematology. 2016; 174(2): 235–248. - Izumi K, Kanda J, Nishikori M, et al. Outcomes of allogeneic stem cell transplantation for DLBCL: a multi-center study from the Kyoto Stem Cell Transplantation Group. Ann Hematol. 2019; 98(12): 2815–2823.
- Herrera AF, Chen Lu, Khajavian S, et al. Allogeneic stem cell transplantation provides durable remission in patients with primary mediastinal large b cell lymphoma. Biol Blood Marrow Transplant. 2019; 25(12): 2383–2387.
- Zurko J, Ramdial J, Shadman M, et al. Allogeneic transplant following CAR T-cell therapy for large B-cell lymphoma. Haematologica. 2023; 108(1): 98–109.
- Fried S, Shouval R, Walji M, et al. Allogeneic hematopoietic cell transplantation after chimeric antigen receptor T cell therapy in large B cell lymphoma. Transplant Cell Ther. 2023; 29(2): 99–107.
