LY-01. Clinical outcomes of allogeneic hematopoietic stem cell transplantation in classical Hodgkin lymphoma

Summary

Patients with classical Hodgkin lymphoma (HL) can achieve a durable remission after initial therapy even with the advanced-stage disease. However, patients with relapsed or refractory HL have a dismal prognosis (rrHL). Current therapeutic options, such as brentuximab vedotin and immune checkpoint inhibitors may improve overall results, but their potential to cure patients is limited and the risk of relapse is still high. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a promising option for these patients. Despite increasing evidence of a clinical benefit of allo-HSCT, many issues remain unresolved. The aim of this study was to investigate the outcomes of allo-HSCT in patients with rrHL in a single center.

Patients and methods

We performed a retrospective analysis of the results of allo-HSCT in 92 patients with rrHL performed between 2002 and 2019 in Raisa Gorbacheva Research Institute (CIC 725). The median age was 30 years (18-49). The median number of prior lines of therapy was 7 (3-12). The median time from diagnosis to transplantation was 44 months (12-129 months). Most of the patients previously undergone an autologous transplantation (n=55, 58%). Forty-eight patients (52%) had primary resistant disease. Objective response determined as complete response (CR) or partial response (PR) before allo-HSCT was documented in 46 (79%) patients (30 CR-52%, 16 PR-27%) and 12 (21%) patients had stable disease (SD)/disease progression (PD). Before allo-HSCT, patients received various therapy options: 39 (42%) patients received brentuximab vedotin based therapy, 26 patients (29%) received immune checkpoint inhibitors and the remaining patients (n=27, 29%) received chemotherapy as a salvage therapy. Twenty-two patients (26%) received transplants from HLA-matched siblings, 54 patients (59%) – from HLA-matched unrelated donors, and haploidentical donors were used in 16 patients (17%). The majority of patients in the general group (n=63, 73%) received reduced intensity conditioning: fludarabine 30 mg/m², bendamustine 130 mg/m² per day for 3 days (FluBe). The GVHD prophylaxis based on posttransplant cyclophosphamide was used in 70 patients (73%).

Results

At the time of analysis, the median follow-up of surviving patients after allo-HSCT was 28 months (1-30). Overall (OS) and progression-free survival (EFS) at 2 years were 74% and 52%, respectively. The cumulative relapse rates and non-relapse mortality were 28% and 20%, respectively. Disease status before the transplantation have a significant impact on OS and EFS: patients who underwent transplantation in complete remission demonstrated the best results: OS at 2 years was 92% versus 67% for PR and 55% for SD/PD (p <0.001); EFS at 2 years was 74% versus 41% for RR and 34% for SD/PD (p <0.001). Patients with FluBe conditioning regimen and the GVHD prophylaxis with cyclophosphamide, as well as the use of new drugs (Brentuximab vedotin or nivolumab) also showed an advantage both in OS: 90% and 83% versus 53% (p=0.001), and EFS: 75% and 71% versus 22% (p <0.001).

Conclusion

Allo-HSCT is a feasible option in rrHL. The use of conditioning regimens with reduced toxicity, cyclophosphamide-based GVHD prophylaxis and new drugs before transplantation can significantly improve the results of allo-HSCT. Pretransplant status at the moment of transplantation was the risk factor showing significant impact on clinical outcomes.

Keywords

Hodgkin lymphoma, hematopoietic stem cell transplantation, allogeneic, pretransplant status, outcomes.