ASCO 2015

Obinutuzumab doubles remission duration in patients with relapsed, indolent non-Hodgkin lymphoma

Dr Laurie Helen Sehn - BC Cancer Agency, Vancouver, Canada

You’ve been looking at indolent non-Hodgkin’s lymphoma, in what setting and why did you try a new agent that basically works in a similar manner to rituximab?

The results that I’m presenting here at ASCO are the primary results of the GADOLIN study. The GADOLIN study investigated the combination of a novel anti-CD20 monoclonal antibody called obinutuzumab in combination with bendamustine versus bendamustine alone for patients who were proven to be refractory to rituximab. So the study was looking at patients who were already relapsed or refractory to prior therapy and were shown not to benefit from the rituximab.

Could you explain to me what you did in the study then?

The study randomised approximately 400 patients one to one to receive either bendamustine alone or bendamustine and obinutuzumab. Patients who were responding to that combination treatment were able to go on to get obinutuzumab maintenance for up to two years of therapy. The primary endpoint was progression free survival and at a pre-planned interim efficacy analysis the IDMC actually recommended that the study be reported because it had met its primary endpoint.

I have some indication that you had quite a big, a good hazard ratio. What were the figures in fact?

Correct. So with a median follow-up time of 21 months the hazard ratio was 0.55, indicating a 45% reduction in the risk of progression in the combination arm.

What does this mean, do you think, in terms of treating these patients resistant to rituximab?

Importantly the safety profile was very favourable so there was very little difference in toxicity between the arms but certainly a big benefit in terms of efficacy with improved progression free survival that was virtually doubled with the combination. So the study essentially showed that the combination of the novel antibody with the chemotherapy backbone, in this case the chemotherapy was bendamustine, it actually led to more than a year’s benefit in terms of progression free survival. So really a clinically relevant period of time.

And you had sufficient patients and it was statistically significant?

Correct.

What do you mean, then, by saying a clinically relevant or clinically meaningful benefit? How would you, in fact, think of using this agent?

Certainly these patients with indolent lymphoma, they develop resistance over time and they become refractory to our standard therapies. This particular population was a group that was already shown to be refractory to rituximab and when they needed to go on to get to their next treatment the combination of the novel antibody to the chemotherapy backbone, bendamustine, really improved the duration of time that they were able to stay in remission.

What’s your recommendation to doctors, then, coming out of this?

This is the first randomised controlled trial that has actually shown a benefit for novel anti-CD20 monoclonal antibody in patients who are refractory to rituximab. So it really is a novel combination that in patients known to be refractory, that particularly with bendamustine, demonstrates a definite improvement in outcome.

And in terms of medicine that can be practised now, what’s the take home?

So obinutuzumab has been made available because in a prior phase III study it’s already been shown for patients with CLL to provide an advantage in patients receiving chlorambucil. So this is the second broad indication where obinutuzumab now has been shown to be beneficial.

So would you use it now for your patients with rituximab refractory non-Hodgkin’s lymphoma, indolent lymphoma?

Based on the results of this study I’d say there’s a real compelling reason to use it in combination with chemotherapy as it does provide significant improvement in progression free survival.