EHA 2021 | 5-year follow-up of ECHELON-1: brentuximab plus AVD versus ABVD in Hodgkin lymphoma

So, the ECHELON-1 study was a large, randomized study, including more than 1,300 patients with stage three or stage four Hodgkin lymphoma, which ended accrual a long time ago. So, what was presented here at the EHA meeting was the five-year update of patients treated on this study.

Five years after the completion of treatment for advanced stage Hodgkin lymphoma is a point in time when you expect the vast, vast, vast majority of relapses to have occurred. So that means that if you are alive and progression-free at five years, it almost invariably means that you are cured. So clinically, really a meaningful point in time to do an update of this first-line study.

So the study was a randomization between standard treatment with ABVD, which is a backbone therapy in the advanced stage Hodgkin lymphoma, has been for decades, and the experimental arm, which was A+AVD, essentially ABVD with the omission of bleomycin and with the addition of brentuximab vedotin which was already registered and approved for the treatment of relapsed and refractory disease, Hodgkin lymphoma.

So already, the primary analysis of this study showed an advantage in favor of the experimental arm, which was after approximately two years median follow up. So now we have five years of follow-up. And what is found essentially is that the progression-free survival as judged by the investigators still is in favor of the experimental arm with a roughly 7% difference in favor of the experimental arm, 82 versus 75% five-year progression-free survival. So, this difference is being maintained, perhaps even getting a little bit larger with time. So that means that roughly there’s a 30% reduction in the risk of failing first-line therapy with the experimental arm as compared to the standard ABVD arm. So, this is one interesting thing, not a great surprise, we’ve seen the same PFS difference in updates after three and four years of the median follow-up.

What is really new is also an analysis of some of the side effects after treatment. One prominent side effect of brentuximab vedotin is sensory peripheral neuropathy and also motor neuropathy. And this certainly is something which occurs with higher frequency and higher severity in the experimental arm than in the standard arm, even though it’s also a problem in the standard arm, despite the absence of brentuximab vedotin.

So, what is seen after five years is a continued improvement of peripheral neuropathy in those patients who had that problem during or after therapy. So, patients continue to experience complete resolution of the neuropathy symptoms, and those who still have remaining symptoms, generally experience improvement of those symptoms, which is really encouraging that these symptoms can get better even after three, four and now five years of follow-up.

Also, the abstract and the presentation gave data on other side effects. One that had not been presented in the previous updates from this study. One is on secondary malignancies. There are second or secondary malignancies have been recorded in patients in both treatment arms. But it’s clear that there is certainly not a higher rate of secondary malignancies in the experimental arm, even though there’s no statistical analysis per se. 19 secondary malignancies in the experimental arm versus 29 in the standard arm. So certainly, if there is a difference, it’s in favor of the experimental arm, but we can’t say that there’s a true difference, but certainly there’s no difference in favor of the standard arm.

And then the last important analysis is an analysis of fertility and successful pregnancies. And in this analysis, we see that there is no difference to be recorded either. Actually, there are in actual numbers, more pregnancies of female patients and pregnancies and new-born babies of partners of male patients, female partners, male patients. So also, here it’s encouraging to see that A+AVD does not harm fertility in those patients. It’s already well-known that ABVD can be given to young female and male patients without compromising fertility significantly, but this is now shown to be also the case for A+AVD, which is really encouraging since it’s a new standard of care for the treatment of advanced stage Hodgkin lymphoma.