Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Độ an toàn và hiệu quả của kháng thể đơn dòng chống chương trình chết tế bào-1 trước và sau cấy ghép tế bào gốc huyết học từ người cho cho bệnh Hodgkin đã tái phát hoặc kháng trị: một nghiên cứu hồi cứu đa trung tâm
Tóm tắt
Chúng tôi đã tiến hành một nghiên cứu đa trung tâm về kháng thể đơn dòng chống chương trình chết tế bào-1 (anti-PD-1 mAbs) trước và sau khi cấy ghép tế bào gốc huyết học từ người cho (allo-HCT) cho bệnh nhân Hodgkin lymphoma. Anti-PD-1 mAbs đã được sử dụng cho 25 bệnh nhân trước khi thực hiện allo-HCT và cho 20 bệnh nhân sau khi cấy ghép. Trong giai đoạn trước allo-HCT, khoảng thời gian trung bình từ lần truyền cuối đến allo-HCT là 59 ngày. Sau khi thực hiện allo-HCT, 12 bệnh nhân đã phát triển hội chứng sốt không do nhiễm trùng cần sử dụng corticosteroid liều cao. Tỷ lệ tích lũy của bệnh ghép chống chủ (aGvHD) độ II–IV là 47,1%. Tám bệnh nhân đã được dự phòng GvHD bằng cyclophosphamide sau cấy ghép (PTCy) có tần suất aGvHD thấp hơn (độ II–IV, 14,6% so với 58,8%; P = 0,086). Tỷ lệ sống sót tổng quát (OS), tỷ lệ tái phát/tiến triển và tỷ lệ tử vong không do tái phát trong 1 năm là 81,3%, 27,9% và 8,4%. Trong giai đoạn sau allo-HCT, khoảng thời gian trung bình từ allo-HCT đến lần truyền đầu tiên là 589 ngày. Tỷ lệ đáp ứng tổng thể và tỷ lệ đáp ứng hoàn toàn lần lượt là 75% và 40%. Tại 100 ngày sau liệu pháp anti-PD-1, tỷ lệ tích lũy của aGvHD độ II–IV, GvHD mãn tính trung bình đến nặng, và độ độc tính liên quan đến miễn dịch độ 3–4 lần lượt là 15,0%, 30,0% và 30,0%. Trong khi tỷ lệ tái phát/tiến triển trong 1 năm là 47,4%, xác suất sống sót trong 1 năm là 89,7%. Tóm lại, các biến chứng liên quan đến miễn dịch là thường xuyên xảy ra mặc dù có những điều chỉnh về dự phòng GvHD hoặc liều lượng anti-PD-1 mAbs. Ở những bệnh nhân đã được điều trị bằng anti-PD-1-mAb, dự phòng GvHD dựa trên PTCy có thể hiệu quả.
Từ khóa
#anti-PD-1 mAbs #cấy ghép tế bào gốc huyết học #Hodgkin lymphoma #GvHD #corticosteroid #tế bào miễn dịchTài liệu tham khảo
Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet (Engl). 2002;359:2065–71.
Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, et al. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study—a prospective clinical trial by the Grupo Espanol de Linfomas/Trasplante de Medula Osea (GEL/TAMO) and the lymphoma working party of the European group for blood and marrow transplantation. Haematologica. 2012;97:310–7.
Kako S, Izutsu K, Kato K, Kim SW, Mori T, Fukuda T, et al. The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Am J Hematol. 2015;90:132–8.
Genadieva-Stavrik S, Boumendil A, Dreger P, Peggs K, Briones J, Corradini P, et al. Myeloablative versus reduced intensity allogeneic stem cell transplantation for relapsed/refractory Hodgkin’s lymphoma in recent years: a retrospective analysis of the lymphoma working party of the european group for blood and marrow transplantation. Ann Oncol. 2016;27:2251–7.
Rashidi A, Ebadi M, Cashen AF. Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma: a systematic review and meta-analysis. Bone Marrow Transplant. 2016;51:521–8.
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clini Oncol. 2017;35:2125–32.
Maruyama D, Hatake K, Kinoshita T, Fukuhara N, Choi I, Taniwaki M, et al. Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Cancer Sci. 2017;108:1007–122.
Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase ii checkmate 205 trial. J Clin Oncol. 2018;36:1428–39.
Manson G, Mear JB, Herbaux C, Schiano JM, Casasnovas O, Stamatoullas A, et al. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation. Eur J Cancer (Oxford, England : 1990). 2019;115:47–56.
Manson G, Herbaux C, Brice P, Bouabdallah K, Stamatoullas A, Schiano JM, et al. Prolonged remissions after anti-PD-1 discontinuation in patients with Hodgkin lymphoma. Blood. 2018;131:2856–9.
Merryman RW, Kim HT, Zinzani PL, Carlo-Stella C, Ansell SM, Perales MA, et al. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood. 2017;129:1380–8.
Haverkos BM, Abbott D, Hamadani M, Armand P, Flowers ME, Merryman R, et al. PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood. 2017;130:221–8.
Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H, et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. Blood. 2017;129:2471–8.
El Cheikh J, Massoud R, Abudalle I, Haffar B, Mahfouz R, Kharfan-Dabaja MA, et al. Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma. Bone Marrow Transplant. 2017;52:1074–7.
Kuno M, Ito A, Tanaka T, Inamoto Y, Kurosawa S, Kim SW, et al. Severe immune-related complications early after allogeneic hematopoietic cell transplantation for nivolumab-pretreated lymphoma. Bone Marrow Transplant. 2019;54:473–6.
Herbaux C, Merryman R, Devine S, Armand P, Houot R, Morschhauser F, et al. Recommendations for managing PD-1 blockade in the context of allogeneic HCT in Hodgkin lymphoma: taming a necessary evil. Blood. 2018;132:9–16.
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.
Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.
Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27:893–8.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21:389–401.el.
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology clinical practice guideline. J Clin Oncol. 2018;36:1714–68.
Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European society for blood and marrow transplantation. Bone Marrow Transplant. 2016;51:906–12.
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;32:3059–68.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.
Nieto JC, Roldan E, Jiménez I, Fox L, Carabia J, Orti G, et al. Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) induces a more tolerant immune response after allogeneic hematopoietic cell transplantation (Allo-HCT) in patients previously exposed to nivolumab. Blood. 2018;132:3402.
Schoch LK, Cooke KR, Wagner-Johnston ND, Gojo I, Swinnen LJ, Imus P, et al. Immune checkpoint inhibitors as a bridge to allogeneic transplantation with posttransplant cyclophosphamide. Blood advances. 2018;2:2226–9.
De Philippis C, Legrand-Izadifar F, Bramanti S, Giordano L, Montes de Oca C, Dulery R, et al. Checkpoint inhibition before haploidentical transplantation with posttransplant cyclophosphamide in Hodgkin lymphoma. Blood advances. 2020;4:1242–9.
Oran B, Garcia-Manero G, Saliba RM, Alfayez M, Al-Atrash G, Ciurea SO, et al. Posttransplantation cyclophosphamide improves transplantation outcomes in patients with AML/MDS who are treated with checkpoint inhibitors. Cancer. 2020;126(10):2193–205.
Kanakry CG, Bolanos-Meade J, Kasamon YL, Zahurak M, Durakovic N, Furlong T, et al. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017;129:1389–93.
Greco R, Lorentino F, Morelli M, Giglio F, Mannina D, Assanelli A, et al. Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation. Blood. 2016;128:1528–31.
Holtick U, Chemnitz JM, Shimabukuro-Vornhagen A, Theurich S, Chakupurakal G, Krause A, et al. OCTET-CY: a phase II study to investigate the efficacy of post-transplant cyclophosphamide as sole graft-versus-host prophylaxis after allogeneic peripheral blood stem cell transplantation. Eur J Haematol. 2016;96:27–35.
Martinez C, Gayoso J, Canals C, Finel H, Peggs K, Dominietto A, et al. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin lymphoma: a registry study of the lymphoma working party of the european society for blood and marrow transplantation. J Clin Oncol. 2017;35:3425–32.
Mariotti J, Devillier R, Bramanti S, Sarina B, Furst S, Granata A, et al. T cell-replete haploidentical transplantation with post-transplantation cyclophosphamide for Hodgkin lymphoma relapsed after autologous transplantation: reduced incidence of relapse and of chronic graft-versus-host disease Compared with HLA-identical related donors. Biol Blood Marrow Transplant. 2018;24:627–32.
Mariotti J, Devillier R, Bramanti S, Giordano L, Sarina B, Furst S, et al. Peripheral blood stem cells versus bone marrow for T Cell-Replete haploidentical transplantation with post-transplant cyclophosphamide in hodgkin lymphoma. Biol Blood Marrow Transplant. 2019;25:1810–7.
Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98:2942–7.
Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64.
Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164–73.
Soiffer RJ, Kim HT, McGuirk J, Horwitz ME, Johnston L, Patnaik MM, et al. Prospective, randomized, double-blind, phase iii clinical trial of anti-t-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017;35:4003–111.
Kobayashi T, Guo YM, Yamashita T, Nara M, Yoshioka T, Kameoka Y, et al. Relationship between clinical course of nivolumab-related myositis and immune status in a patient with Hodgkin's lymphoma after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2019;109:356–60.
Blasig H, Bender C, Hassel JC, Eigentler TK, Sachse MM, Hiernickel J, et al. Reinduction of PD1-inhibitor therapy: first experience in eight patients with metastatic melanoma. Melanoma Res. 2017;27:321–5.
Martini DJ, Lalani AA, Bosse D, Steinharter JA, Harshman LC, Hodi FS, et al. Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: a case series. J Immunother Cancer. 2017;5:66.
Fujita K, Uchida N, Kanai O, Okamura M, Nakatani K, Mio T. Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: emerging reports of 12 cases. Cancer Chemother Pharmacol. 2018;81:1105–9.
