Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma

• Type of Material: Article
• Authors: Pamela B Allen, Emory University; Xinyan Lu, Northwestern University; Qing Chen, Northwestern University; Kaitlyn O'Shea, Northwestern University; Joan S Chmiel, Northwestern University; Liron Barnea Slonim, Northwestern University; Madina Sukhanova, Northwestern University; Hatice Savas, Northwestern University; Andrew M Evens, Rutgers Cancer Institute of New Jersey; Ranjana Advani, Stanford University; Barbara Pro, Northwestern University; Reem Karmali, Northwestern University; Brett Palmer, Northwestern University; Robert A Bayer, Northwestern University; Robert M Eisner, Northwestern University; Eric Mou, Stanford University; Gary Dillehay, Northwestern University; Leo I Gordon, Northwestern University; Jane N Winter, Northwestern University
• Language: English
• Date: 2023-06-16
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2022008116
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 7
• Issue: 12
• Start Page: 2670
• End Page: 2676
• Keywords: Life Sciences & Biomedicine; BLOCKADE; NIVOLUMAB; BRENTUXIMAB VEDOTIN; Hematology; Science & Technology
• Research Categories: Engineering, Biomedical; Health Sciences, Oncology

Abstract

In a multicenter, phase 2, investigator-initiated trial of sequential pembrolizumab and AVD (doxorubicin, vinblastine, and dacarbazine), nearly two-thirds of patients with untreated, unfavorable, or advanced-stage classic Hodgkin lymphoma (cHL) achieved positron emission tomography (PET)–defined, complete or near-complete metabolic responses (CMRs), following pembrolizumab monotherapy. Furthermore, all patients achieved CMR after 2 cycles of AVD, with 100% of patients alive and without relapse at initial publication. We now report long-term follow-up, including the 3-year overall survival (OS) and planned correlative analyses. Thirty patients received 3 cycles of single-agent pembrolizumab, followed by AVD chemotherapy for 4 to 6 cycles depending on the stage and bulk. PET/computed tomography 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 programmed cell death protein 1 (PD-1) pathway markers. At a median follow-up of 33.1 months (range, 26.0-43.0), progression-free survival and OS remained 100%. All patients had genomic alterations in 9p24.1 and were positive for programmed death ligand 1 (PD-L1) by immunohistochemistry. There was no relationship between depth of response to single-agent pembrolizumab and 9p24.1 alterations or PD-1 pathway H-scores. After additional follow-up, sequential pembrolizumab and AVD remained highly effective. The high response rates observed at all PD-L1 levels suggest that even low levels of PD-L1 expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase 2 trial (registered at www.clinicaltrials.gov as #NCT03226249) is ongoing to confirm our findings.