Sequential Pembrolizumab and AVD is Highly Effective at any PD-L1 Expression Level in Untreated Hodgkin Lymphoma.

In a multicenter, phase II investigator-initiated trial of sequential pembrolizumab and AVD, nearly two-thirds of patients with untreated unfavorable or advanced stage classic Hodgkin Lymphoma (cHL) achieved PET-defined complete or near complete metabolic responses (CMR) following 3 doses of pembrolizumab monotherapy. Furthermore, all achieved CMR following 2 cycles of AVD chemotherapy and 100% of patients were alive without relapse at the time of initial publication. We now report long-term follow-up, including 3-year OS and planned correlative analyses. Thirty patients received single agent pembrolizumab every 3 weeks x 3, followed by AVD chemotherapy for 4-6 cycles depending on stage and bulk. PET/CT scan was performed after pembrolizumab monotherapy, 2 cycles of AVD, and at the end of therapy. Baseline biopsy samples were analyzed for genomic alterations of chromosome 9p24.1 and PD-1 pathway markers by immunohistochemistry. At a median follow up of 33.1 months (range, 26.0-43.0), PFS and OS remain 100%. All patients had genomic alterations in 9p24.1 and were positive for PD-L1 by immunohistochemistry. There was no relationship between response to single agent pembrolizumumab measured by decline in metabolic tumor volume and 9p24.1 alterations or PD-1 pathway H-scores. With additional follow-up, sequential pembrolizumab and AVD remains highly effective. The high response rates observed at all PD-ligand levels suggest that even low levels of PD ligand expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase II trial (NCT05008224) to confirm these findings is ongoing.