Pembrolizumab vs brentuximab vedotin in relapsed or refractory classic Hodgkin lymphoma

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Published: 16 Jun 2020
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Dr John Kuruvilla - Princess Margaret Cancer Centre, Toronto, Canada

Prof John Kuruvilla speaks to ecancer about the results from the KEYNOTE-204 trial that were presented at the ASCO 2020 Virtual Meeting.

The phase III trial was a randomised, open-label study of pembrolizumab vs brentuximab vedotin in relapsed or refractory classic Hodgkin lymphoma.

Prof Kuruvilla reports that pembrolizumab had a statistically significant and clinically meaningful improvement in progression-free survival.

 

KEYNOTE-204 was a randomised international phase III open-label study in patients with relapsed or refractory classical Hodgkin’s lymphoma that was testing the experimental treatment pembrolizumab, an anti-PD1 antibody, versus brentuximab vedotin, an anti-CD38 antibody-drug conjugate. The trial included patients that had relapsed post-autologous stem cell transplant or were ineligible for autologous stem-cell transplant but had received at least one prior line of treatment. The primary endpoint of the study was progression free survival and when you look at the main results of the clinical trial pembrolizumab had a statistically significant and clinically meaningful improvement in progression free survival with a hazard ratio of 0.65 and a median progression free survival of 13 months for the pembrolizumab treated patients compared to a little over 8 months for the patients that received brentuximab vedotin. When you look at all of the other endpoints of the trial they all favour pembrolizumab, whether it’s duration of response, overall response rate, though it did not reach statistical significance. It’s still a little too early to look at the impact of these treatments on overall survival in this patient population but we will be aiming to show that at further follow-up.

The toxicity data from the clinical trial was quite consistent with what we know about both drugs, so just to highlight the typical thing that we see with brentuximab is peripheral neuropathy, which is generally well managed. What we see with pembrolizumab are the common immune toxicities that we see with this class of drug. It’s important to recognise that these are generally quite mild and well tolerated and can be managed very straightforwardly. But we did see pneumonitis in a little over 10% of patients, 5% of these patients experienced this with a grade 3/4 toxicity. The patients on this study were generally managed with corticosteroids. There were no treatment related deaths with the drug-related pneumonitis and patients were largely quite well and had these symptoms resolve over time.

The conclusion of this study, based on this favourable efficacy and well tolerated, was that pembrolizumab should represent the new standard as a therapy for patients in this setting with relapse post-transplant or those ineligible for stem cell transplant.

KEYNOTE-204 had a couple of different stratification factors that were built in to the clinical trial. The first one looked at the presence or absence of prior autologous stem cell transplant; the second stratification factor was how patients had responded to primary treatment and duration of remission. So there were three categories of patients – patients that were primary refractory to front line therapy, patients with early relapse within twelve months of completion of treatment and patients with later relapse beyond twelve months. Looking at the subgroup analyses that were done to look at the primary endpoint, progression free survival, this effect was seen quite consistently over all of those subgroups, whether they had had an autologous stem cell transplant or not. In addition, if patients had disease that was primary refractory at relapse early versus relapse late.

Lastly, just to highlight prior brentuximab vedotin was not an exclusion for this clinical trial because people had understood that brentuximab had moved earlier in the treatment algorithm of Hodgkin’s lymphoma based on other randomised trials. It’s now used in the curative setting in a multiple of settings using different treatments. So for that reason there were a small number of patients that had had prior brentuximab therapy. When looking at those patients compared to those who were treatment naïve, the treatment in fact favouring pembrolizumab was still present and significant.