Mogamulizumab demonstrates significant improvement in progression free survival for CTCL

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Published: 10 Dec 2017
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Dr Steven Horwitz - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Horwitz speaks with ecancer at the 2017 ASH annual meeting about results from the phase III MAVORIC study, looking at mogamulizumab versus vorinostat in patients with previously treated cutaneous T-cell lymphoma.

He highlighted that in the first report evaluating progression free survival as a primary endpoint in cutaneous T-cell lymphoma, mogamulizumab demonstrated significantly superior progression free survival, overall response rate, and quality of life compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma.

Read the news story for more. 

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

Cutaneous T-cell lymphoma is an uncommon form of lymphoma, it presents primarily in the skin or often in the blood, in which case we call it Sézary syndrome. Those are a group of diseases which tend to be chronic, they have a high burden of symptoms for patients because the disease is on your skin. We have treatments that create responses but rarely long-term durable responses and cures are really only seen in the setting of very aggressive therapy like allogeneic stem cell transplantation. So it’s basically treated like a chronic lymphoma where we look for active therapies to control the disease, improve quality of life, but also a key feature is that those treatments be able to be given on a long-term basis without cumulative toxicities to really try to control the disease for as long as possible.

What did you look at in this study?

The MAVORIC study was investigating the activity of a drug called mogamulizumab against a standard, in this case vorinostat which is a standardly used treatment in the US. Mogamulizumab is a monoclonal antibody targeted to CCR4 which is a chemokine receptor that happens to be highly expressed on patients’ tumour cells with Sézary syndrome and with mycosis fungoides. Mogamulizumab is already approved in Japan in cutaneous T-cell lymphoma, peripheral T-cell lymphoma and HTLV-1 associated lymphoma so there’s a fair amount of experience in safety with this. In some earlier phase II studies done outside of Japan there was particularly good activity in cutaneous T-cell lymphoma, particularly the Sézary syndrome population. So in trying to advance that understanding and really pin down where that drug would fit MAVORIC was a large randomised international study looking at mogamulizumab against a standard of care option like vorinostat.

The primary endpoint was progression free survival but really all measures of clinical benefit were looked at, including response, duration of response, impact on quality of life, side effects etc., all the things that we think are important in this disease.

How many patients?

It was over 300 patients so this is really the largest randomised study against a standard that has ever been done in cutaneous T-cell lymphoma.

What have you found so far?

The results really show very good activity for mogamulizumab. Compared to vorinostat mogamulizumab had higher progression free survival which was the primary endpoint, there were also higher rates of response, improvement in quality of life. It looks like the drug can be given safely over a long period of time in this population without cumulative side effects so it fits that need to provide some durable benefit in the patients who respond. So it really looked like a more powerful, more active drug than vorinostat in this study.

What sort of side effects are we seeing?

It’s a monoclonal antibody, the main side effects have been infusion related side effects, so infusion reactions which are usually manageable, and that’s been the main side effect.

What conclusions can you come to?

The main conclusion of this study is that really at the primary and the secondary endpoints mogamulizumab looks more effective than vorinostat which again is the standard drug. So the hope is that this will lead to approval because the drug is not currently available in the US. If it is then we’ll factor that in to our treatment armamentarium. So it will definitely be an additional tool, there are certain patient populations, particularly the Sézary population where we often struggle with active drugs, that this may move pretty high up on the algorithm. Then the other hope for the future when we think about a monoclonal antibody with good activity and safety is could we think about ways to partner this with other combinations so we can maybe move beyond palliative chronic treatment for these diseases and really try to get more patients into deeper remissions longer.

Will you be looking at overall survival?

Overall survival is a tricky endpoint in this disease because patients get multiple therapies over time and it’s really a chronic disease. So it will be looked at as an exploratory endpoint in this study but that may take a long time to develop and it’s a hard endpoint to interpret when patients have so many different therapies over the time. But that data could be interesting.