Checkpoint inhibitor‐based salvage regimens prior to autologous stem cell transplant improve event‐free survival in relapsed/refractory classic Hodgkin lymphoma

Abstract

Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p < .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.

Overall survival of patients with cHL who progress after autologous stem cell transplant: results in the novel agent era

“…With increasing evidence that pre-ASCT CPI–based salvage therapies is associated with higher post-ASCT PFS, earlier use of CPI as a salvage regimen before ASCT could improve outcomes in this high-risk population. 7 , 19 …”

“… 2 , 3 , 4 Patients who are refractory to frontline therapy, who relapse within 1 year of frontline chemotherapy, who have pre-ASCT positive positron emission tomography (PET) scan, and who require multiple lines of salvage therapy are at particularly higher risk of disease relapse after ASCT. 5 , 6 , 7 Patients who relapse after ASCT have traditionally had poor prognosis with a median survival of 2 to 3 years in the pre–novel agent era. 8 , 9 …”

“…Addition of novel agents, particularly brentuximab vedotin (BV) and checkpoint inhibitors (CPI) have shown encouraging response and survival in frontline and relapsed refractory disease. 1 , 7 , 10 , 11 , 12 , 13 BV, combined with Adriamycin, dacarbazine, and vinblastine, has improved progression-free survival (PFS) and overall survival of cHL compared with longstanding standard of care chemotherapy regimen consisting of Adriamycin, vinblastine, bleomycin, and dacarbazine. 1 In R/R cHL, salvage regimen incorporating BV and/or CPI has shown encouraging outcomes with 2-year PFS up to 97%.…”

“… 10 , 14 CPI-based regimens are associated with higher post-ASCT PFS than conventional savage chemotherapy in retrospective studies. 7 …”

Immune checkpoint inhibitors in advanced and relapsed/refractory Hodgkin lymphoma: current applications and future prospects

“…An alternative ICI, tislelizumab, was designed to overcome one of the mechanisms behind PD-PD-L1 pathway blockade resistance, antibody-dependent cellular phagocytosis, by minimizing binding to the cellular receptor on macrophages ( 46 – 48 ). In the phase 2 trial of tislelizumab monotherapy, the results were notable for an overall response rate of 87.1%, complete response rate of 62.9%, and median duration of response of 31.3 months, as detailed in Table 1 ( 45 ).…”