Allogeneic stem cell transplantation; lymphoma; non Hodgkin lymphoma; primary mediastinal B cell lymphoma; Adult; Humans; Retrospective Studies; Remission Induction; Recurrence; Hematopoietic Stem Cell Transplantation/adverse effects; Graft vs Host Disease/etiology; Lymphoma, B-Cell/therapy; Lymphoma, B-Cell/complications; Hematology; Oncology; Radiology, Nuclear Medicine and Imaging; General Medicine
Abstract :
[en] Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting.Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined.Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured.Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.
Disciplines :
Hematology
Author, co-author :
Le Calvez, Baptiste ; Hématologie Clinique, CHU Hôtel Dieu, Nantes, France
Tessoullin, Benoit; Hématologie Clinique, CHU Hôtel Dieu, Nantes, France
Renaud, Loïc; AP-HP, Hôpital Saint-Louis, Hemato-oncologie, DMU DHI, Université de Paris, Paris, France
Botella-Garcia, Carmen; Hématologie Clinique, CHU de Bordeaux, Bordeaux, France
Srour, Micha; Maladie du sang, CHU de Lille, Lille, France
Le Gouill, Steven; Hématologie Clinique, CHU Hôtel Dieu, Nantes, France
Guillerm, Gaelle; Hématologie Clinique, CHU de Brest, Brest, France
Gressin, Rémy; Hématologie Clinique, CHU de Grenoble, Grenoble, France
Nguyen Quoc, Stéphanie; Hématologie Clinique, Hôpital Pitié Salpêtrière, Paris, France
Furst, Sabine; Hématologie Clinique, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France
Chauchet, Adrien; Hématologie Clinique, CHU de Besançon, Besançon, France
Sibon, David; Hématologie Clinique, Hôpital Necker-Enfants Malades, Paris, France
Lewalle, Philippe; Hématologie Clinique, Hôpital J. Bordet, Bruxelles, Belgium
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.
Savage KJ, Monti S, Kutok JL, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical hodgkin lymphoma. Blood. 2003; 102 (12): 3871–3879.
Abou-Elella AA, Weisenburger DD, Vose JM, et al. Primary mediastinal large B-Cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska lymphoma study group. J Clin Oncol. 1999; 17 (3): 784–90790.
Giulino-Roth L. How I treat primary mediastinal B-cell lymphoma. Blood. 2018; 132 (8): 782–790.
Vitolo U, Seymour JF, Martelli M, et al. Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016; 27: 91–102.
Cwynarski K, Marzolini MAV, Barrington SF, et al.; British Society for Haematology Guidelines. The management of primary mediastinal B‐cell lymphoma: a british society for haematology good practice paper. Br J Haematol. 2019; 185 (3): 402–409.
Camus V, Rossi C, Sesques P, et al. Outcomes after first-line immunochemotherapy for primary mediastinal B-cell lymphoma: a LYSA study. Blood Adv. 2021; 5 (19): 3862–3872.
Wästerlid T, Hasselblom S, Joelsson J, et al. Real-world data on treatment and outcomes of patients with primary mediastinal large B-cell lymphoma: a swedish lymphoma register study. Blood Cancer J. 2021; 11 (5): 100.
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.
Eule C, Arora N, Hsiao C, et al. Presentation and management of primary mediastinal large B-cell lymphoma: a retrospective cohort analysis. Acta Oncol. 2020; 59 (7): 786–788.
Giulino‐Roth L, O’Donohue T, Chen Z, et al. Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R. Br J Haematol. 2017; 179 (5): 739–747.
Soumerai JD, Hellmann MD, Feng Y, et al. Treatment of primary mediastinal B-cell lymphoma with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone is associated with a high rate of primary refractory disease. Leuk Lymphoma. 2014; 55 (3): 538–543.
Aoki T, Shimada K, Suzuki R, et al. High-dose chemotherapy followed by autologous stem cell transplantation for relapsed/refractory primary mediastinal large B-cell lymphoma. Blood Cancer J. 2015; 5 (12): e372-e372.
Kuruvilla J, Pintilie M, Tsang R, et al. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma. 2008; 49 (7): 1329–1336.
Vardhana S, Hamlin PA, Yang J, et al. Outcomes of relapsed and refractory primary mediastinal (thymic) large B cell lymphoma treated with Second-Line therapy and intent to transplant. Biol Blood Marrow Transplant. 2018; 24 (10): 2133–2138.
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.
Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-Cell lymphoma. N Engl J Med. 2017; 377 (26): 2531–2544.
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.
Crombie JL, Nastoupil LJ, Redd R, et al. Real-world outcomes of axicabtagene ciloleucel in adult patients with primary mediastinal B-cell lymphoma. Blood Adv. 2021; 5 (18): 3563–3567.
Fenske TS, Ahn KW, Graff TM, et al. Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation. Br J Haematol. 2016; 174 (2): 235–248.
Bacher U, Klyuchnikov E, Le-Rademacher J, et al. Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity? Blood. 2012; 120 (20): 4256–4262.
Glass B, Hasenkamp J, Wulf G, et al. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014; 15 (7): 757–766.
Le Bourgeois A, Labopin M, Blaise D, Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, et al. Reduced-intensity versus reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted non-Hodgkin lymphoma adult patients: a retrospective study on behalf of the. Ann Oncol. 2017; 28 (9): 2191–2198.
Herrera AF, Chen L, 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.
Cheson BD, Pfistner B, Juweid ME, International Harmonization Project on Lymphoma, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25 (5): 579–586.
Cheson BD, Fisher RI, Barrington SF, United Kingdom National Cancer Research Institute, 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): 3059–683068.
Ruggeri A, Labopin M, Ciceri F, et al. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP–EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016; 51 (4): 610–611.
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.
Martin PJ, Lee SJ, Przepiorka D, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-Host disease: VI. The 2014 clinical trial design working group report. Biol Blood Marrow Transplant. 2015; 21 (8): 1343–1359.
International Non-Hodgkin’s lymphoma prognostic factors project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993; 329 (14): 987–994.
Carbone PP, Kaplan HS, Musshoff K, et al. Report of the committee on hodgkin’s disease staging classification. Cancer Res. 1971; 31 (11): 1860–1861.
Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017; 130 (3): 267–270.
Schuster SJ, Bishop MR, Tam CS, JULIET Investigators, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-Cell lymphoma. N Engl J Med. 2019; 380 (1): 45–56.
Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. The Lancet. 2020; 396 (10254): 839–852.
Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019; 20 (1): 31–42.
Hamadani M, Gopal AK, Pasquini M, et al. Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis. Blood Adv. 2022; 6 (2): 486–494.
Shah NN, Hamadani M. Is there still a role for allogeneic transplantation in the management of lymphoma. J Clin Oncol. 2021; 39 (5): 487–498.
Dreger P, Fenske TS, Montoto S, European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR), et al. Cellular immunotherapy for refractory diffuse large B cell lymphoma in the chimeric antigen receptor-engineered T cell era: still a role for allogeneic transplantation? Biol Blood Marrow Transplant. 2020; 26 (4): e77–e85.
Shadman M, Gauthier J, Hay KA, et al. Safety of allogeneic hematopoietic cell transplant in adults after CD19-targeted CAR T-cell therapy. Blood Adv. 2019; 3 (20): 3062–3069. 22
Zoellner A-K, Fritsch S, Prevalsek D, et al. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma. Bone Marrow Transplant. 2015; 50 (5): 679–684.
Garciaz S, Castagna L, Bouabdallah R, et al. Familial haploidentical challenging unrelated donor Allo-SCT in advanced non-Hodgkin lymphomas when matched related donor is not available. Bone Marrow Transplant. 2015; 50 (6): 865–867.
Mariotti J, Devillier R, Bramanti S, 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 (3): 627–632.
Gauthier J, Poiré X, Gac A-C, et al. Better outcome with haploidentical over HLA-matched related donors in patients with hodgkin’s lymphoma undergoing allogeneic haematopoietic cell transplantation—a study by the francophone society of bone marrow transplantation and cellular therapy. Bone Marrow Transplant. 2018; 53 (4): 400–409.
Schmid C, Schleuning M, Schwerdtfeger R, et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood. 2006; 108 (3): 1092–1099.
Duléry R, Ménard A-L, Chantepie S, et al. Sequential conditioning with thiotepa in T Cell- Replete hematopoietic stem cell transplantation for the treatment of refractory hematologic malignancies: Comparison with matched related, Haplo-Mismatched, and unrelated donors. Biol Blood Marrow Transplant. 2018; 24 (5): 1013–1021.
Kolb H-J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008; 112 (12): 4371–4383.
Guillaume T, Porcheron S, Audat F, et al. Recommandations de la SFGM-TC concernant l’injection prophylactique, préemptive et curative des lymphocytes du donneur (DLI) après allogreffe de cellules souches hématopoïétiques. Pathol Biol. 2014; 62 (4): 193–196.
