Good afternoon everybody. My name is Mhairi Copland from the University of Glasgow and I’m presenting this data on behalf of Professor Richard Clark from the University of Liverpool. I’m presenting the data from the British DESTINY study. There are three critical questions at the moment in chronic myeloid leukaemia – how to predict which patients are going to transform to an acute leukaemia; how to manage side effects in patients and to identify which patients with good responses are able to discontinue therapy. Many studies have already shown that it is safe to stop therapy in those patients who are optimally responding and have undetectable levels of BCR-ABL which is the gene that is abnormal in chronic myeloid leukaemia. What we wanted to explore in the DESTINY study was the potential of cutting the dose of tyrosine kinase inhibitor therapy in CML by half followed by stopping therapy in patients not just with undetectable disease but also with stable low levels of disease. We hypothesised that more patients would be able to reduce therapy safely and a proportion of these would be able to go on to stop therapy and also that the patients on half dose therapy would have a reduced amount of side effects compared to those on full dose therapy.

Entry into the DESTINY clinical trial was allowed for patients that not only had undetectable disease, which we called MR4 but also patients that had low levels of detectable disease which we called MR3. The patients in the trial, once they were entered, halved their dose of tyrosine kinase inhibitor therapy and they could be on either imatinib, nilotinib or dasatinib. We recruited 174 patients to the study. Of the 174 patients, 93% of patients on half dose therapy showed no evidence of leukaemia gene recurrence within twelve months. We had twelve molecular relapses, which was defined as loss of MR3 on two consecutive samples, so we showed that the leukaemia gene was rising in these patients and this occurred between the second and the twelfth month of reduction of therapy.

We split the patients into two groups: those that had undetectable disease which was MR4 at study entry, which was 125 patients, and those that had low levels of detectable disease which we called MR3. Of those in the MR3 group 18.4% relapsed at a median of 4.4 months from reducing the dose of therapy; for those in the MR4 group with undetectable disease 2.4% of patients relapsed and the median time to relapse was longer at 8.7 months. This is depicted graphically here, just showing the relapse free survival in both patient groups and we can see that the levels of relapse in both groups that halved therapy is low but the level of relapse is much less in the MR4 group which had undetectable levels of the leukaemia gene.

When we went on to re-treat patients with full dose tyrosine kinase inhibitors when they demonstrated recurrence of the leukaemia gene all patients in both the MMR group and the MR4 group recovered within 4 months to very low levels of disease.

We wanted to understand the effect that reducing the dose of the tyrosine kinase inhibitor would have on TKI related symptoms over time and these plots, at 12 o’clock we have the baseline levels of symptoms, and we can see that as patients proceed through their therapy within the first three months of therapy patients had significant reductions in lots of different side effects, including lethargy, diarrhoea, rash, nausea, oedema and hair thinning. So these all improved within the first three months of reducing their dose of therapy but thereafter there was no further improvement in the symptoms over time.

We’ve also done a financial analysis of halving the dose of treatment and within the 174 patients the halving treatment saved £1.9 million in the UK from an expected TKI budget of £4.1 million which is a 46.7% saving and there were similar levels of savings between the MR4 group, so the group with undetectable levels of the leukaemia gene, and those with low levels of leukaemia.

I’d like to acknowledge funding from Bloodwise and from the University of Newcastle. I’d also like to acknowledge the CML patients and the teams that contributed patients. Thank you.