Pretransplant promise for PD-1 in Hodgkin lymphoma

In this issue of Blood, Desai et al¹ represent the largest retrospective analysis to date, evaluating programmed death protein-1 inhibitor (PD-1i)–based regimens as salvage therapy, administered prior to autologous stem cell transplantation (ASCT), in patients with relapsed or refractory classical Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) is an uncommon, but highly curable cancer accounting for 10% of all lymphomas. However, almost 15% to 30% of patients with late-stage disease will relapse or have primary refractory disease.² The standard of care for eligible patients has traditionally included salvage chemotherapy followed by ASCT, resulting in metabolic complete remission rates of up to 50%.³

Nearly 1300 patients across 6 centers were included, predominantly from retrospective cohorts, with ∼20% treated within clinical trials. Although fewer than one-quarter received PD-1i–based regimens before ASCT, this group still represented 315 patients. The majority received PD-1i in combination with chemotherapy (41%) or brentuximab vedotin (BV; 40%). Within the chemotherapy-only arm, ifosfamide, carboplatin, and etoposide was the most common regimen used (46%), followed by gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (5.6%).

The findings are compelling. The use of PD-1i–based salvage was associated with superior 2-year progression-free survival (PFS) compared with those receiving BV or chemotherapy alone (88.2% vs 70.2% vs 67.4%; P< .0001). An association with overall survival (OS) advantage was observed primarily among patients who achieved complete metabolic response following PD-1i therapy compared with BV or chemotherapy alone. Importantly, 2-year OS remained high across all groups (99.0% vs 97.6% vs 94.3%, respectively). A comparison between pembrolizumab and nivolumab was not performed. The authors appropriately adjusted for pretransplant prognostic variables across treatment groups in this retrospective analysis. Few prospective studies have examined PD-1i–based salvage regimens in relapsed/refractory cHL undergoing ASCT. Existing data are limited to small single-arm phase 2 trials, all showing similarly impressive overall response rates and 2 to 3-year PFS/OS (see table).