The Management of Relapsed Hodgkin´s Lymphoma after Haploidentical Stem Cell Transplantation: Donnor Lymphocyte Infusion and Brentuximab Vedotin

Introduction

Despite the high cure rate of Hodgkin lymphoma (HL) with conventional radiochemotherapy, HL is refractory in 15% to 30% of patients. In those patient who relapse or refractory to chemotherapy Allogeneic transplantation (alloSCT) will be an option, despite the promising results the rate of relapse is higher. In this situation there is not standardized treatment, we hypothesized that treatment with Brentuximab Vedotin (BV) in combination with donor lymphocyte infusion (DLI) would be a promising approach for relapsed HL after alloSCT that selectively targets lymphoma cells and enhances the graft versus leukemia (GvL) response by the induction of immunogenic cell death.

Material and method

Between 2014-2016 we studied 6 patients who were relapses of HL after haploSCT, we designed a treatment algorithm combining BV infusions during 6 cycles (1.8 mg/kg per day every 21 days) with donor DLI)administration in escalate dosis 1x10e4/kg CD3, increasing 1 log for dosis in an alternating regimen after the third cycles of BV. We stop the DLI when GVHD appear or toxicity, we perform a PET-CT after the first 3 cycles BV, after ILD + 6 cycles BV and 3 month after finish the treatment designed. We analisis safety, complication an side effect of the combination. The aim of this study was to retrospectively evaluate the efficacy and safety of BV + DLI in HL relapsing or progressing after allo-SCT.

Results

A total of 4 patients (66%) were nodular sclerosis histological subtype and 34% (2 patients) was linfocitic predominance. The median age was 32 years (22-48). Median follow-up was 837 days (405-975). The median of treatment lines received before transplantation was 6 (4-7). Only 2 patients (34%) had reached haploTPH in complete remission.Peripheral blood was used as progenitors source in 66% (6). The median time to relapse was 286 days (range 180-463). 5 patients (83%) received BV before alloSCT, only 2 (34%) achieved CR.

All the patients relapse after the alloSCT, then we decide began the designed treatment, after the first 3 cycles of BV, 17% (1 patients) was in CR. After that we associated DLI in all the cases, the median was 8 (3-13) plus another 3 cycles of BV, after this in the reevaluation CR was observed in 50% (3 patients). When combined radiotherapy (RT) in selected cases, CR rate was 100% in the PET-CT 3 month after finish the treatment designed. The combination DLI + BV was without important toxicity. Acute GVHD was observed in 83% (5 patients) the 100% was grade I-II. 66% (4 patients) developed chronic GVHD, 100% was limited extension. Treatment with BV + DLI resulted in an PFS of 100%.

Conclusions

The combination treatment was well tolerated, confirming a manageable safety profile for BV plus DLI after alloSCT, is an effective and safe therapy to achieve disease control in HL relapsing after alloSCT. We assumed that the combination of BV with DLI will have the potential to further increase the GvL effect. Despite this findings, we need multicentric studies to perform standarized treatments.