Frontline treatment with single agent pembrolizumab followed by AVD chemotherapy for classic Hodgkin lymphoma

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Published: 22 Dec 2021
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Prof Pamela Allen - Emory University School of Medicine, Georgia, USA

Prof Pamela Allen speaks to ecancer about the updated results and correlative analysis of a study investigating frontline treatment with single-agent pembrolizumab (PEM) followed by AVD chemotherapy for classic Hodgkin lymphoma.

Initially, she talks about the background and methodology of the study. Prof Allen then explains the results.

She says that they found that after extended follow-up, sequential pembrolizumab and AVD chemotherapy was a highly effective strategy with 100% of patients remaining alive without relapse.

The high response rates observed at all PD-L1/PD-L2 levels in this clinical study suggest that even low levels of PD ligand expression may be sufficient for response to PD-1 blockade in previously untreated cHL.

She concludes by discussing how these results can improve the treatment of classical Hodgkin lymphoma.



 

Prior to our study we had previously seen excellent results with PD-1 blockade in classic Hodgkin lymphoma with both pembrolizumab and nivolumab demonstrating excellent results. Furthermore there had been additional studies demonstrating a biologic rationale for why there were such high response rates in Hodgkin, specifically there were chromosomal alterations of 9p24.1, which contains the coding regions for PD ligands 1 and 2, and ubiquitous expression of PD ligands on classical Hodgkin Reed-Sternberg cells.

This was a phase II clinical trial, multicentre, performed within the United States at academic centres. We included patients with newly diagnosed either advance stage or early stage unfavourable classic Hodgkin lymphoma. Patients were treated with a total of three doses of pembrolizumab followed by PET imaging for our primary endpoint which was to assess the complete metabolic response rate to a lead-in of single agent pembrolizumab. Patients then went on to receive between four to six cycles of AVD chemotherapy and then had repeat imaging after two cycles as well as at the end of therapy to assess response. At ASH we updated our results with longer progression free and overall survival and also presented our correlative analyses.

With extended follow-up of 33.1 months we found that progression free and overall survival were both 100% with not a single patient progressing or relapsing or dying from their disease during the follow-up period. We also looked at some correlative analyses including 9p24.1 alterations and we looked at FISH for phospho STAT3 as well as PD ligands 1 and 2 to see if either one of these correlated with depth of response. But we did not find that there was any correlation between any of these PD-1 pathway markers and depth of response which ultimately we thought was likely due to the fact that all of our patients had such exquisite responses.

There is now an ongoing larger phase II study, the KEYNOTE-C11, which is going to look at the same study design of sequential pembrolizumab and AVD chemotherapy. The hope is that with continued follow-up we will continue to see the same excellent results and will be able to confirm in a larger cohort whether or not these results are true.

So far these are probably the best results that we have seen in a frontline study and so we’re very excited to see how this will pan out in the larger phase II study