Second Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma after a Previous Autograft: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation
Authors: Martinez Carmen , Boumendil Ariane , Romejko-Jarosinska Joanna , Anagnostopoulos Achilles , Faber Edgar , Poire Xavier , Yakoub-Agha Ibrahim , Akhtar Saad , Gurman Gunhan , Pavone Vincenzo , Halaburda Kazimierz , Botelho Sousa Aida , Ghesquieres Herv , Finel Hervé , Khvedelidze Irma , Montoto Silvia , Sureda Anna 
Published: October 2019

Abstract
Patients with relapsed or refractory (R/R) Hodgkin Lymphoma (HL) after first autologous stem cell transplantation (ASCT1) may be offered several therapeutic options. New agents such as brentuximab vedotin or checkpoint inhibitors have recently been approved for the treatment of these patients, however, their efficacy to provide long-term control or cure is still unknown. Thus, a significant proportion of patients are still considered candidates for a second hematopoietic stem cell transplantation, usually an allogeneic transplantation. A second ASCT (ASCT2) has historically been considered as an option only in a small group of patients so the published experience is scarce.
We retrospectively evaluated the outcome of 56 adult patients (25% female/75% male) with R/R HL registered in the EBMT database who received an ASCT2 between 2005 and 2014. Planned tandem ASCT were excluded. The median age at ASCT2 was 33 years (range, 19-71) and most patients (n=46, 87%) had a Karnofsky performance score ≥80%. Forty (73%) and 9 (16%) patients were in complete remission (CR) and partial remission (PR), respectively, at day 100 after ASCT1. Twenty-six (46%) relapsed within 12 months after ASCT1. Patients received a median of 1 (0-5) treatment lines between ASCT1 and ASCT2. Of note, only 2 patients received brentuximab vedotin after ASCT1 and none of the patients in our series received checkpoint inhibitors as salvage after ASCT1. The median interval from relapse/progression to ASCT2 was 9.7 months (1.7-89.3). At the time of ASCT2, 38 (69%) patients had chemosensitive disease (20 of them CR; and 18 PR). Most patients (n=43, 77%) received BEAM as the conditioning regimen for ASCT1, whereas preparative regimens for ASCT2 were more heterogeneous (BEAM or similar in 27, 48%; CBV or similar in 8, 14%; and others in 21, 37%). The median time to neutrophil (>0.5x109/L) and platelet (>20x109/L) recovery after ASCT2 were 11 (IQR 9-12) and 12 (IQR 10-15) days, respectively. Best response at day 100 following ASCT2 included CR in 29 (52%) patients and PR in 7 (12%); 3 (5%) had stable disease, and 3 (5%) progressed. Twenty-nine (52%) patients are currently alive, with a median follow-up for surviving patients of 73 months (2-153). Causes of death were HL progression (n=21, 79%), ASCT2 toxicity (n=3, 11%), secondary neoplasia (n=1, 3.7%), and unknown (n=2, 7%). The 4-year non-relapse mortality (NRM) was 5% (95% CI 1-14%). The 4-year cumulative incidence of disease progression/relapse was 69% (95% CI 54-80%). The 4-year overall survival (OS) and progression free survival (PFS) were 63% (95% CI 51-77%) and 25% (95% CI 16-41%). In univariate analysis, HL relapse within 12 months of ASCT1 was associated with a worse 4-year OS (44% vs. 79%, p=0.016) and PFS (16% vs. 33%, p=0.033). Chemosensitivity at ASCT2 predicted for better outcomes (4-year OS 78% vs. 30%, p=0.002; PFS 34% vs. 6%, p=0.004).
Our series is the largest thus far reported of ASCT2 for patients with R/R HL after ASCT1. NRM is lower than that observed after allogeneic transplantation in this setting; however, relapse remains a major issue, especially for patients who relapse in less than one year after ASCT. For this population, a second ASCT should not be considered, whereas ASCT2 in patients with long response duration after ASCT1 might be appropriate in selected cases. The role of ASCT2 for those patients treated with new drugs such as brentuximab vedotin and checkpoint inhibitors deserves further investigation.

Disclosures
Martinez: BMS: Research Funding; Takeda: Consultancy. Sureda:BMS: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Merck: Consultancy, Honoraria.