ASH 2015

Ibrutinib to treat elderly patients with chronic lymphocytic leukaemia

Dr Alessandra Tedeschi - Azienda Ospedaliera Niguarda Cà Granda Milano, Milano, Italy

Ibrutinib emerged a few years ago, an interesting drug, and you’re using it in chronic lymphocytic leukaemia now. Can you tell me, what was the issue you wanted to investigate in this disease?

The problem is that the majority of CLL patients are elderly and they have frequent comorbidities and they poorly tolerate the most intensive immunochemotherapeutic regimens. For this reason maybe patients sometimes are under-treated and this prevents them from reaching their potential lifespan. Chlorambucil was considered for years the standard first line treatment for elderly patients because of the comorbidities and there was no other regimen until then that has shown an improvement in overall survival in elderly patients. So ibrutinib, that was an easy to deliver treatment, highly effective and with a safe toxic profile, sounded promising in the treatment of the elderly population.

Could you tell me about the action of ibrutinib and why it was suitable for this category of patients?

The action of ibrutinib is that ibrutinib blocks the B-cell signalling which is important for CLL cells’ proliferation. Blocking the cascade of Bcl signalling we obtain an apoptosis of the CLL clone. Ibrutinib is a targeted therapy, is not a chemotherapy, so importantly doesn’t have all the toxic effects of chemotherapy.

So what did you do in the study?

The study was a comparison and we evaluated the efficacy of ibrutinib compared to chlorambucil, which was considered in this moment the standard of treatment for these patients. It was a randomised trial, enrolled 269 patients, treatment naïve CLL patients 65 years or older.

And what did you find?

We found that ibrutinib significantly improves progression free survival, median progression free survival has been reached with chlorambucil at 19 months and was not reached with patients treated with ibrutinib. Then 18 months progression free survival rate was 90% with ibrutinib versus 45% with chlorambucil. Also ibrutinib significantly prolonged overall survival which is an important matter.

By how much?

At 24 months we have 98% patients still alive with ibrutinib versus 85% with chlorambucil.

Is this drug ready for prime time then, in this setting?

A request has been made to the FDA for treatment of first line treatment. Of course it’s an important new step towards a chemotherapy free treatment for elderly patients and this is a very important issue in this population of frail patients.

Now, it is potentially a more gentle treatment, what were the toxicities with ibrutinib?

Most common toxicities were grade 1 diarrhoea, now they are fatigue. While there were toxicities more common in the chlorambucil arm of course we are dealing with chemotherapy so we had more vomiting, nausea and neutropenia in the chlorambucil arm.

So what’s your interpretation to cancer doctors now about what they should think about this new development?

I think that we are going towards chemotherapy free regimens and this is very important for our patients. It’s important for their quality of life, of course. In the future we have maybe to ameliorate something in the outcome of patients even if it’s difficult to ameliorate the results we obtained in this trial with these frail patients but we have a lot of other agents that could be combined with ibrutinib, like monoclonal antibodies or other targeted therapies to improve outcome.

So what’s your quick take-home message for doctors coming out of your study and your new emerging understanding of treating this category of CLL?

The take-home message is that we have to have hope for our patients and we are going towards chemotherapy free regimens and this is very important. If ibrutinib will be available it would be a very nice treatment for elderly unfit patients.