Brentuximab vedotin prior to allogeneic stem cell transplantation increases survival in chemorefractory Hodgkin’s lymphoma patients
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).
KeywordsHodgkin lymphoma Brentuximab vedotin Allogeneic stem cell transplant
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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 was obtained from all individual participants included in the study.
- 1.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 17:3101–3109CrossRefGoogle Scholar
- 2.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 14:572–578CrossRefGoogle Scholar
- 3.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):3419–3425CrossRefGoogle Scholar
- 4.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 30:2183–2189CrossRefGoogle Scholar
- 5.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):91703–91710CrossRefGoogle Scholar
- 7.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):1817–1824CrossRefGoogle Scholar
- 8.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. 385:1853–1862CrossRefGoogle Scholar
- 9.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 372:311–319CrossRefGoogle Scholar
- 10.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 34:3733–3739CrossRefGoogle Scholar
- 12.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):579–586CrossRefGoogle Scholar
- 13.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):35–40CrossRefGoogle Scholar
- 15.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 32:187–191CrossRefGoogle Scholar
- 17.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):86–96CrossRefGoogle Scholar
- 18.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 129:1380–1388CrossRefGoogle Scholar
- 19.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):3229–3234Google Scholar
- 22.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 94:1337–1343CrossRefGoogle Scholar
- 24.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):1428–1439CrossRefGoogle Scholar
- 25.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):1562–1566CrossRefGoogle Scholar