Allogeneic Stem Cell Transplantation After Reduced Intensity Conditioning (RIC-allo) in Patients with Relapsed or Refractory Hodgkin's Lymphoma (HL). Final Analysis of the HDR-Allo Protocol – A Prospective Clinical Trial by the Grupo Español de Linfomas / Trasplante de Medula Osea (GEL/TAMO) and the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).
Authors: Sureda Anna , Canals Carme , Arranz Reyes , Caballero Dolores , Ribera Josep Maria , Brune Mats L , Passweg Jakob R. , Besalduch Joan , Duarte Rafael F , Leon Angel , Pascual Maria Jesus , Schmitz Norbert 
Published: October 2019

Abstract 658

The HDR-allo trial was a prospective phase II study evaluating the feasibility and safety of RIC-allo in relapsed or refractory HL. Patients (pts) were eligible if they had achieved complete remission (CR), partial remission (PR), or stable disease after salvage chemotherapy. The conditioning regimen consisted of fludarabine (150 mg/m2) and melphalan (140 mg/m2); graft-versus-host disease (GVHD) prophylaxis combined cyclosporine A and short-course methotrexate. From March 2000 to September 2007, 88 pts were included; 10 pts progressed after salvage therapy, 78 pts proceeded to RIC-allo. There were 49 males, the median age was 32 (range: 18-55) years at the time of RIC-allo. 70 pts had failed > 2 lines of therapy, 68 pts had received radiotherapy, and 67 pts (86%) had failed a prior autograft (ASCT). Median time from diagnosis to RIC-allo was 46 (range: 9-300) months, median time to progression from ASCT was 8 (range: 2-144) months. 52 pts were allografted with sensitive disease (CR or PR), the remaining 28 pts were grafted with resistant disease. A matched sibling donor was available in 55 pts (70%), a matched unrelated donor (MUD) was used in 23 pts; the MUD pts received ATG (90 mg/kg) as additional GVHD prophylaxis. Stem cells were derived from peripheral blood in 75 pts. Cumulative incidence of non-relapse mortality (NRM) was 15% and 19% at 1 and 3 years, respectively, it was adversely influenced by poor performance status (ECOG ≤ 2) [relative risk 3.9, 95% confidence interval (CI) 1.8–7.3, p = 0.05] and refractory disease at the time of transplant [relative risk 2.6, 95%CI 1.5–4.5, p = 0.01]. Cumulative incidence of acute GVHD was 32% at 100 days, cumulative incidence of chronic GVHD (cGVHD) was 40% and 44% at 1 and 2 years, respectively. The development of cGVHD was significantly associated with a reduced relapse rate (36% vs 60%, p = 0.05). With a median (range) time to relapse of 6 (3–35) months, relapse rate was 37% and 59% at 1 and 3 years, respectively. Having failed > 3 lines of therapy and refractory disease at the time of transplant were independent adverse prognostic factors (p = 0.03 and p = 0.01, respectively). With a median follow up of 38 (range: 12-69) months, PFS was 50% and 25% at 1 and 3 years, respectively. It was adversely influenced by refractory disease at the time of RIC-allo (64% for sensitive vs. 25% for refractory pts at 1 year, p < 0.001). OS was 71% and 43% at 1 and 3 years, respectively. It also was significantly lower in pts with refractory disease (80% in sensitive vs. 56% in refractory pts at 1 year). 25 pts received donor lymphocyte infusions (DLI). 14 pts received DLI alone; in 9 pts a combination with chemotherapy was given. Response rate (CR/PR) was 40% for patients receiving DLI alone and 53% for those receiving the combination. No differences in any outcome parameter were observed between sibling and MUD transplants. In conclusion, RIC-allo is a feasible and relatively safe procedure also in heavily pretreated HL patients. Results are more promising in pts with chemosensitive disease at transplantation (64% PFS at 1 year). No difference was observed between patients allografted from HLA-identical siblings or MUD. The lower relapse rate in pts developing cGVHD, the response rate of 43% after DLI, and the existence of long-term disease free survivors are all indicators of a clinically relevant graft-versus-HL effect. The high relapse rate remains the major clinical problem. More intense (intermediate) conditioning and RIC-allo earlier in the course of disease will be evaluated in further studies.

Disclosures:

No relevant conflicts of interest to declare.