Ibrutinib is a Bruton’s tyrosine kinase inhibitor currently approved in the United States by the FDA for treatment of patients with chronic lymphocytic leukaemia and mantle cell lymphoma. It has rationale to be studied in multiple myeloma as well. The Bruton’s tyrosine kinase is expressed in primary myeloma cell samples from patients with myeloma. Also it is a drug that can modulate the environment of the cell including the bone microenvironment and other cells in the microenvironment to favourably impact multiple myeloma.

So a good idea to try using it but could you tell me what you did in the study, the protocol?

Sure. In this study we looked at various dose levels of the drug. It was a phase II study but there were four different cohorts starting the drug at a dose level between 420mg to 840mg a day with or without dexamethasone. The drug in the study showed at the highest dose level that there was activity with 25% of patients having a clinical benefit and another 25% of patients having stable disease for four months or more. Most of these patients had been exposed to a variety of immunomodulatory drugs and also proteasome inhibitors. Most of them had had a stem cell transplant. Most of them had had dexamethasone before. To see this signal of activity is encouraging.

Could you give me some kind of idea, though, of how significant this signal is, the numbers of patients and the differences you obtained?

There were about 15-20 odd patients in each cohort and the signal that we obtained is significant in that in a heavily pre-treated patient population for a single drug to have prolonged disease stabilisation and minimal responses does merit further study of the drug with other combinations including proteasome inhibitors and immunomodulatory drugs. A trial with carfilzomib is currently on-going and other trials with other proteasome inhibitors and immunomodulatory drugs are planned.

Do you have any ideas about the mechanisms that might give you clues as to how to develop this as a therapy in pre-treated myeloma but also, perhaps, earlier in the disease?

The drug, as I have mentioned, has got activity both directly, potentially, on the multiple myeloma cell and on cells in the microenvironment of the cancer cell that support its growth. It is felt that the true potential of the drug lies in combination therapy with active drugs like immunomodulatory drugs and proteasome inhibitors.

What should doctors be understanding from this fairly early study but interesting one?

They should stay tuned for further updates with larger cohorts of patients and looking at the combination data as it emerges in future trials.

So what do you think are the prospects for using this targeted therapy, ibrutinib, in the future in multiple myeloma and perhaps elsewhere? It’s already established in other applications, isn’t it?

This is the first report of the drug so I think one needs to see more data before one can conclusively answer a question as to where this drug will ultimately end up in the therapeutic paradigm of multiple myeloma.

And to summarise, the take home message of what you have discovered so far is what?

The take home message is that the drug had activity with both patients having minimal response and prolonged disease stabilisation in single agent and in combination with dexamethasone in this trial.