Combination of Brentuximab Vedotin and Pembrolizumab as Salvage Treatment Before Autologous Stem Cell Transplantation and Maintenance in Patients with Relapsed/Refractory Hodgkin Lymphoma

Background: In relapsed or refractory classical Hodgkin lymphoma, achieving complete remission on 18FDG PET-CT before autologous stem cell transplantation improves progression-free survival. However, the optimal salvage therapy to achieve this remains undefined. Brentuximab vedotin combined with PD1 inhibitors has shown promise, though limited data exist on the combination of brentuximab vedotin and pembrolizumab. Methods: We retrospectively collected data from 24 adult patients with confirmed relapsed or refractory classical Hodgkin lymphoma, who started salvage treatment with brentuximab vedotin and pembrolizumab with the intention of consolidation with high-dose chemotherapy, followed by autologous stem cell transplantation and brentuximab vedotin maintenance. Results: After two cycles of brentuximab vedotin and pembrolizumab, 95.2% achieved an overall response and 81.0% achieved complete metabolic response. 20 patients (83.3%) were in complete response at the end of maintenance, of whom one relapsed at 28 months after the end of treatment. Grade 3 and 4 toxicities during salvage treatment consisted mainly of hematological toxicity, one thyrotoxicosis, one hemophagocytic lymphohistiocytosis, and one arthralgia. Non-hematological grade 3-4 toxicities following transplantation were an inflammatory pneumonitis and one cryptococcal meningitis. One death occurred during prolonged post-transplant aplasia. During maintenance, dose reductions for toxicity were necessary in 16 patients, mainly due to peripheral neuropathy. Conclusions: For heavily pretreated relapsed or refractory classical Hodgkin lymphoma patients, our data suggest that salvage therapy with brentuximab vedotin and pembrolizumab before autologous stem cell transplantation followed by brentuximab vedotin maintenance is a highly active strategy, with acceptable toxicities. Further studies with larger cohorts are necessary to confirm these data.