Efficacy of Reduced-Intensity Allogeneic Stem Cell Transplant after Brentuximab Vedotin in Patients with Hodgkin Lymphoma Relapsed after Autologous Transplant
Authors: Zallio Francesco , Busca Alessandro , Mordini Nicola , Fornaro Maria jose , Bruno Benedetto , Catania Gioacchino , Salvi Flavia , Parvis Guido , Ladetto Marco , Pini Massimo 
Published: October 2019

Abstract
Purpose: The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous stem cell transplantation (ASCT) is generally poor, because salvage chemo-radiotherapy is able to produce only short-lasting remissions. In a previous study on a large patients' population (Sarina B et al, Blood 2010) was clearly demonstrated that the availability of a donor could significantly improve survival outcomes after allogeneic transplant, in particular for the subset of patients who reach a status of pre-transplant complete remission; however the application of this procedure is actually limited by a difficulty to obtain an objective response before alloSCT. It was recently shown that Brentuximab vedotin, a new generation antibody-drug conjugate, is able to induce nearly 30% of complete remission in HL patients relapsing after autologous transplant; therefore this agent could effectively work in relapses after ASCT as a platform to allow a better disease control in order to improve the outcome of the allografting procedure.
Aims: Aim of this study was to retrospectively investigate if brentuximab vedotin administered as a salvage therapy in HL patients relapsing after ASCT could improve the efficacy of a subsequent reduced-intensity allogeneic transplant.
Methods: Between August 2011 and September 2013, 11 patients underwent to allo-SCT at four hematologic Divisions of Northern Italy for HL relapse after ASCT, after brentuximab vedotin administered as a bridge to the allografting procedure. Median age was 32 years (range 21-61) and median number of prior regimens was 5, including ASCT. Patients received a median of 6 cycles (range 4-7) of brentuximab vedotin administered every 3 weeks as a 30-minute outpatient IV infusion; median time between the last dose of brentuximab vedotin and the allo-SCT was 1 month (range 1-5 months). No patient experienced progression during treatment with brentuximab vedotin (4 complete remissions and 7 partial remission/stable disease). All but one patients did not have a HLA identical sibling, so they required a matched unrelated (6 patients), haploidentical donor (3 patients) or cord blood (1 patient); peripheral stem cells were the source in patients with HLA identical sibling or unrelated, whereas bone marrow was used in the haplo setting. Reduced-intensity was the conditioning regimen performed in all patients. Post transplant cyclophosphamide plus mycophenolate mofetil/tacrolimus was the graft-versus-host disease (GVHD) prophylaxis of the haplo setting, while Metotrexate/cyclosporine was administered in the other patients. Patients were monitored for engraftment and infectious complications per institutional standards; survival outcomes were defined according to the European Blood and Marrow Transplantation (EBMT) criteria for survival analysis.
Results: One patient had primary graft failure with autologous reconstitution; she was a patient with a high body-mass index, in whom the drug's doses of the conditioning regimen were underestimated in order to avoid excessive toxicity. All the other patients engrafted; median time to neutrophil recovery was 20 days (range 15-26). At a median follow-up of 12 months, the 2-year progression free survival was 51%, 2-year Overall Survival was 61%. There were 2 toxic deaths, one for EBV reactivation and one for leuko-encefalopathy disease, resulting in a 2-year non-relapse mortality of 18%.
Conclusions: These data suggest that brentuximab vedotin represents a promising salvage therapy in HL patients relapsed after ASCT. Despite the bias concerning the differences in source of stem cells and pre-transplant conditioning regimens, we showed that brentuximab could be administered in patients who are candidates to a RIC allo-SCT, with encouraging survival outcomes. Further clinical trials with larger number of patients and longer follow-up are recommended to confirm the promising role of brentuximab as a bridge to alloSCT.

Disclosures
No relevant conflicts of interest to declare.