Abstract
This study reports a retrospective multicenter experience by the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patients characteristics and outcomes of 21 brentuximab vedotin (BV)–pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) without prior BV. In total, 72 patients with classical Hodgkin’s lymphomas who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or the incidence and severity of acute graft versus host disease (GVHD). Indeed, a lower incidence of chronic GVHD was observed in the BV group, with a 43% cumulative incidence at 3 years versus 47% in the no BV group, although this was not statistically significant. Despite the low incidence of chronic GVHD, survival was not worse in the BV-treated group: 3-year progression-free survival (PFS) was 53%, 3-year overall survival (OS) was 62%, 3-year non-relapse mortality (NRM) was 24%. In the no BV group, the 3-year PFS was 33%, 3-year OS was 44%, and 3-year NRM was 14%. In chemorefractory patients at the time of transplant, we found a statistically significant difference in PFS between the BV and no BV groups (51% vs. 10%, p = 0.013).
Similar content being viewed by others
References
Sweetenham JW, Carella AM, Taghipou G, Cunningham D, Marcus R, Della Volpe A et al (1999) High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin’s disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. J Clin Oncol 17:3101–3109
Gajewski JL, Phillips GL, Sobocinski KA, Armitage JO, Gale RP, Champlin RE, Herzig RH, Hurd DD, Jagannath S, Klein JP, Lazarus HM, McCarthy PL Jr, Pavlovsky S, Peterson FB, Rowlings PA, Russell JA, Silver SM, Vose JM, Wiernik PH, Bortin MM, Horowitz MM (1996) Bone marrow transplants from HLA-identical siblings in advanced Hodgkin’s disease. J Clin Oncol 14:572–578
Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A (2011) BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood 118(12):3419–3425
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30:2183–2189
Pellegrini C, Broccoli A, Pulsoni A, Rigacci L, Patti C, Gini G, Mannina D, Tani M, Rusconi C, Romano A, Vanazzi A, Botto B, Santoro A, Hoaus S, Rigolin GM, Musto P, Mazza P, Molica S, Corradini P, Fama A, Gaudio F, Merli M, Ronconi F, Gritti G, Vallisa D, Tosi P, Liberati AM, Pinto A, Pavone V, Gherlinzoni F, Bianchi MP, Volpetti S, Trentin L, Goldaniga MC, Bonfichi M, De Renzo A, Schiavotto C, Spina M, Carella AM, Stefoni V, Argnani L, Zinzani PL (2017) Italian real life experience with brentuximab vedotin: results of a large observational study on 234 relapsed/refractory Hodgkin’s lymphoma. Oncotarget 8(53):91703–91710
Forero-Torres A, Fanale M, Advani R, Bartlett NL, Rosenblatt JD, Kennedy DA, Younes A (2012) Brentuximab vedotin in transplant-naive patients with relapsed or refractory hodgkin lymphoma: analysis of two phase I studies. Oncologist 17:1073–1080
Pavone V, Mele A, Carlino D, Specchia G, Gaudio F, Perrone T, Mazza P, Palazzo G, Guarini A, Loseto G, Eleonora P, Cascavilla N, Scalzulli P, Melpignano A, Quintana G, Di Renzo N, Tarantini G, Capalbo S (2018 Oct) Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP). Ann Hematol 97(10):1817–1824
Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J (2015) Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo controlled, phase 3 trial. Lancet. 385:1853–1862
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319
Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH (2016) Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol 34:3733–3739
Sureda A, Domenech E, Schmitz N et al (2014) The role of allogeneic stem cell transplantation in Hodgkin’s lymphoma. Curr Treat Options in Oncol 15:238–247
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V, International Harmonization Project on Lymphoma (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586
Gaudio F, Mazza P, Carella AM, Mele A, Palazzo G, Pisapia G, Carluccio P, Pastore D, Cascavilla N, Specchia G, Pavone V (2019) Outcomes of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for Hodgkin lymphomas: a retrospective multicenter experience by the Rete Ematologica Pugliese (REP). Clin Lymphoma Myeloma Leuk 19(1):35–40
Chen R, Palmer JM, Thomas SH, Tsai NC, Farol L, Nademanee A, Forman SJ, Gopal AK (2012) Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood 119:6379–6381
Garciaz S, Coso D, Peyrade F, Fürst S, Duran S, Chetaille B, Brenot-Rossi I, Devillier R, Granata A, Blaise D, Bouabdallah R (2014) Brentuximab vedotin followed by allogeneic transplantation as salvage regimen in patients with relapsed and/or refractory Hodgkin’s lymphoma. Hematol Oncol 32:187–191
Hegerova L, Cao Q, Lazaryan A, McClune BL, Weisdorf DJ, Brunstein CG, Bacha- nova V (2017) Improving outcomes after allogeneic hematopoietic cell transplantation for Hodgkin lymphoma in the brentuximab vedotin era. Bone Marrow Transplant 52:697–703
Bazarbachi A, Boumendil A, Finel H, Mohty M, Castagna L, Peggs KS, Blaise D, Afanasyev B, Diez-Martin JL, Sierra J, Bloor A, Martinez C, Robinson S, Malladi R, El-Cheikh J, Corradini P, Montoto S, Dreger P, Sureda A (2018 Apr) Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party. Br J Haematol 181(1):86–96
Merryman RW, Kim HT, Zinzani PL, Carlo-Stella C, Ansell SM, Perales MA, Avigdor A, Halwani AS, Houot R, Marchand T, Dhedin N, Lescaut W, Thiebaut-Bertrand A, Francois S, Stamatoullas-Bastard A, Rohrlich PS, Labussiere Wallet H, Castagna L, Santoro A, Bachanova V, Bresler SC, Srivastava A, Kim H, Pesek E, Chammas M, Reynolds C, Ho VT, Antin JH, Ritz J, Soiffer RJ, Armand P (2017) Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood 129:1380–1388
Agrawal B, Reddish M, Longenecker BM (1996) CD30 expression on human CD8+ T cells isolated from peripheral blood lymphocytes of normal donors. J Immunol 157(8):3229–3234
Muta H, Boise LH, Fang L, Podack ER (2000) CD30 signals integrate expression of cytotoxic effector molecules, lymphocyte trafficking signals, and signals for proliferation and apoptosis. J Immunol 165:5105–5111
Chiarle R, Podda A, Prolla G, Gong J, Thorbecke GJ, Inghirami G (1999) CD30 in normal and neoplastic cells. Clin Immunol 90(2):157–164
Malard F, Bossard C, Brissot E, Chevallier P, Guillaume T, Delaunay J, Mosnier JF, Mor- eau P, Gregoire M, Gaugler B, Mohty M (2013) Increased plasmacytoid dendritic cells and RORgammat-expressing immune effectors in cutaneous acute graft-versus-host disease. J Leukoc Biol 94:1337–1343
Chen YB, McDonough S, Hasserjian R, Chen H, Coughlin E, Illiano C, Park IS, Jagasia M, Spitzer TR, Cutler CS, Soiffer RJ, Ritz J (2012b) Expression of CD30 in patients with acute graft-versus-host disease. Blood 120:691–696
Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM (2018) 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 36(14):1428–1439
Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, Fong A, Younes A (2016 Sep 22) Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 128(12):1562–1566
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Human and animal rights
This article does not contain any studies with animals performed by any of the authors.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Gaudio, F., Mazza, P., Mele, A. et al. Brentuximab vedotin prior to allogeneic stem cell transplantation increases survival in chemorefractory Hodgkin’s lymphoma patients. Ann Hematol 98, 1449–1455 (2019). https://doi.org/10.1007/s00277-019-03662-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-019-03662-6