Primary results from the MABLE phase IIIb study

Dr Anne-Sophie Michallet - Centre Hospitalier Lyon-Sud, Lyon, France

The MABLE study is a multi-centre randomised study and the background is you know in CLL the combination of rituximab, fludarabine and cyclophosphamide is the standard of care but many CLL patients are elderly, with comorbidity, and we have shown a study with good results with a combination of rituximab bendamustine and rituximab chlorambucil. So the MABLE study is very important because it studies the efficacy and the safety of the combination of rituximab bendamustine versus chlorambucil for CLL patients ineligible for fludarabine best therapy.

Can you tell me a bit about the results and the response rates and the safety?

Yes. The results are so very important, actually. Immunotherapy, the study is difficult actually, I know. So the result was the combination of rituximab bendamustine is good with higher CR rates versus chlorambucil. For the rate it’s 24% for the bendamustine versus 9% for the combination of chlorambucil. The overall response rate is similar and the PFS, the progression free survival, is also higher for the bendamustine, with 39.6 months for bendamustine versus 29.9 months for the combination of chlorambucil. So we have an extended PFS with this combination of bendamustine of ten months. For the safety, good safety for the two arms with slightly higher grade 3 adverse events for the bendamustine arm driven for blood disorders. We have a few neutropenia and also a higher rate of infection, 12% for bendamustine versus 10% for chlorambucil.

And how many patients were involved in this trial?

357 patients randomised and we have first line patients and second line. For the first line 121 for bendamustine and 120 for chlorambucil. The two arms were balanced when we considered characteristics of the patient and prognostic factors.

And what do you think the next steps in your research will be?

It’s very difficult because we know we are in the new drug era and what is the place of this combination of bendamustine. But I think for patients, elderly patients or comorbid patients, this combination of rituximab bendamustine looks like a good first line option.

Is there any take home message you’d like to give?

Because bendamustine is good, it’s safe, and if you have to make something for a CLL patient, an elderly CLL patient or unfit, you can use this option. Or if you want to choose another, for example the combination of rituximab chlorambucil you have to use chlorambucil at high doses like in the MABLE study versus in CLL11.