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Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma
Abstract   Open access   Peer reviewed

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

Pamela B. Allen, Xinyan Lu, Qing Chen, Kaitlyn O’Shea, Joan S. Chmiel, L. Barnea Slonim, M. Sukhanova, Hatice Savas, Andrew M. Evens, Ranjana Advani, …
Blood advances
09/09/2022
DOI: 10.1182/bloodadvances.2022008116
PMCID: PMC10333742
PMID: 36083129
url
https://doi.org/10.1182/bloodadvances.2022008116View
Published (Version of record) Open Access

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 3 doses of pembrolizumab monotherapy. Furthermore, all patients achieved CMR after 2 cycles of AVD chemotherapy, and 100% of the patients were alive without relapse at the time of initial publication. We now report the long-term follow-up, including the 3-year overall survival (OS) and planned correlative analyses. Thirty patients received single-agent pembrolizumab 3 times every 3 weeks, 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 by immunohistochemistry. 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 response to single-agent pembrolizumab measured by a decline in metabolic tumor volume 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 programmed death ligand levels suggest that even low levels of programmed death ligand 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. [Display omitted] •One hundred percent of patients remain alive without relapse following sequential pembrolizumab and AVD after nearly 3 years of follow-up.•PD-1 pathway correlatives were not associated with the depth of response to PD-1 blockade.

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