ECHELON-2: Study into brentuximab vedotin and CHP versus CHOP in the frontline treatment of patients with T-Cell lymphomas

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Published: 6 Dec 2018
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Dr Lorenz Trümper - Georg August University, Göttingen, Germany

Dr Lorenz Trümper speaks to ecancer at ASH 2018 about the study of brentuximab vedotin and CHP versus CHOP in the treatment for peripheral T-Cell lymphoma patients.

He explains that brentuximab vedotin targets the CD30 antigen that is very specific to T-Cell lymphomas.

Dr Trümper reports that the treatment with brentuximab vedotin has already provided a superior strong difference in progression free survival.

I’m reporting about the ECHELON-2 trial. This is a trial in patients with peripheral T-cell lymphoma. Peripheral T-cell lymphoma is a) a rare disease and b) a disease with inferior prognosis when you compare it to the much more prevalent B-cell lymphomas. Progress in B-cell lymphomas has mainly been achieved by adding antibodies to the standard treatment, in this case it was Rituxan. The prognosis of patients with peripheral T-cell lymphoma is inferior by 15-20%, as opposed to patients with B-cell lymphoma and we’ve all been looking for drugs, for new drugs, that improve the outcome of those patients.

Now, when you look at the T-cell lymphomas, one of the surface antigens that is very specific to certain subtypes is the CD30 or Ki-1 antigen which was discovered about 35 years ago by Harris, Stein and Keale and this antigen can be targeted by an antibody. Previous trials that have used a naked antibody without any attachments have not been very successful – they have not improved outcome of patients. So when brentuximab vedotin came along and showed that the outcome of patients treated with that drug in relapse were superior to any other treatment we were very excited about that. Brentuximab vedotin is a drug where the CD30 antibody is coupled to a cytostatic drug, MMAE, so this drug is being delivered directly to the tumour cells. A previous trial in relapsed patients had shown that 84% of those patients who were refractory to standard treatment responded to brentuximab vedotin.

Now the ECHELON trial has done a very simple step forward now. We are comparing CHOP, the standard treatment, with brentuximab vedotin added to CHOP. One difference – we have to omit oncovin from the CHOP treatment because oncovin is very similar in its mode of action to the vedotin, to the chemotherapy part of our ADC.

This trial randomised in a one to one fashion 226 patients to each arm, so a large number of patients from all over the world – United States, Canada, Europe, Asian countries – and it’s being presented now. Much to our surprise and fulfilling some of the hopes for our patients, there was a very strong difference in progression free survival of 13% and already at this point in time in overall survival. So it’s really exciting to see this because the ECHELON trial is the first ever phase III frontline trial in T-cell lymphoma where we have shown an improvement in outcome. I think this will lead to a new standard of care in this subtype of lymphomas.

What is the message for doctors watching this?

The message is two things – when you have a patient with T-cell lymphoma you send the slides to a specialised pathologist and you ask this pathologist to stain for CD30. If it’s an anaplastic large cell lymphoma with CD30 on the surface the new standard of treatment, standard of care in treatment, will be Adcetris plus CHOP. There are some other lymphomas that have a lower percentage of CD30 positive cells and in these instances you should consult with a specialist in this disease if adding Adcetris makes sense or not.