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Multicenter Study
. 2023 Jun 27;7(12):2670-2676.
doi: 10.1182/bloodadvances.2022008116.

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

Pamela B Allen  1 , Xinyan Lu  2 , Qing Chen  2 , Kaitlyn O'Shea  2 , Joan S Chmiel  2 , Liron Barnea Slonim  2 , Madina Sukhanova  2 , Hatice Savas  2 , Andrew M Evens  3 , Ranjana Advani  4 , Barbara Pro  2   5 , Reem Karmali  2 , Brett Palmer  2 , Robert A Bayer  2 , Robert M Eisner  2 , Eric Mou  4   6 , Gary Dillehay  2 , Leo I Gordon  2 , Jane N Winter  2
Affiliations
Multicenter Study

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

Pamela B Allen et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: J.N.W. reports research funding from Merck, and an honorarium for an advisory board and for her spouse’s consultancy with an honorarium from Novartis, CVS Caremark, and Epizyme. L.I.G. reports honorarium from Janssen Data and advisory boards (Safety Monitoring Board) with Bristol Myers Squibb, Gilead/Kite, and Xylem Cofounder Inc. R.A. reports institutional research funding from Merck and advisory board and consultancy for Merck. A.M.E. reports honorarium for advisory boards with Seattle Genetics. B. Pro reports honorarium for advisory boards with Seattle Genetics. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Kaplan-Meier analysis. (A) PFS; (B) OS.
Figure 2.
Figure 2.
Baseline PD-L1 expression and correlation to single-agent pembrolizumab response. (A-C) PD-1 pathway correlates baseline PD-L1/PAX-5 staining by immunohistochemistry (A), PD-L1 H score distribution across a cohort of 29 patients (B), and association between PET responses to single-agent pembrolizumab and PD-L1 H score in baseline biopsy specimens (C).
See this image and copyright information in PMC

References

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