PracticeUpdate: Haematology & Oncology

ASH 2016 19

Reducing or stopping a TKI can be safe and beneficial for some patients with CML R esults of two trials have found no evidence of relapse in a large propor- tion of patients with chronic myeloid The other important implication is that patients do not have to have extremely

stopping tyrosine kinase inhibition, 62% showed no evidence of leukaemia recurrence at 6 months, and half (52%) showed no re- currence at 24 months. Of patients who experienced molecular recur- rence, most regained their previous remission level after resuming tyrosine kinase inhibi- tion, and no study participants progressed to a dangerous state of advanced disease. Mhairi Copland, MD, PhD, of the University of Glasgow in the UK, set out to study a co- hort of patients with CML from the British Destiny Study who decreased their dose of TKI. Dr Copland and colleagues found that many patients with CML may be able to safely re- duce side effects of tyrosine kinase inhibition by cutting their dose in half. In contrast to other trials, which have focused on patients nearly free of leukaemia, the Brit- ish Destiny Study included patients with a stable molecular remission level demarcated as molecular response 3, “good, but not per- fect,” said Dr Copland. The results suggest that a wider range of pa- tients may be able to safely reduce tyrosine kinase inhibition than previously thought. Of 174 study participants, the vast majority (93%) showed no evidence of leukaemia rebound 1 year after cutting their dose of tyrosine kinase inhibitor. Many reported a significant decrease in associated side effects within the first 3 months. Twelve participants showed signs of leukae- mia recurrence, all of whom regained a remis- sion level of molecular response 3 or better within 4 months of resuming a full dose. Dr Copland said, “Taken together, these findings might indicate that some patients are being unnecessarily overtreated. The other important implication is that patients do not have to have extremely low levels of leukaemia on very sensitive tests to safely try reducing their dose of tyrosine kinase inhibitor.” Participants who started with the extremely low level of molecular-response 4 leukaemia were significantly less likely to experience a leukaemia rebound (2.4%) than those classi- fied as molecular response 3 (18.4%). The low rates of rebound suggest it is safe for molecular response 3 patients to attempt to reduce their dose of tyrosine kinase inhibitor. Any benefits in terms of reducing side effects should become apparent within the first 3 months.

leukaemia 1–2 years after discontinuing or reducing the dose of a tyrosine kinase inhib- itor. These outcomes of the EURO-SKI Trial and the British Destiny Study were reported at ASH 2016. Francois-Xavier Mahon, MD, PhD, of Uni- versity of Bordeaux, France, explained that thanks to tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, and dasatinib, the life expectancy of patients with chronic myeloid leukaemia (CML) now approaches that of the general population. TKIs are so effective at controlling CML that some patients seek to avoid side effects and save costs by reducing the dose or discontinuing tyrosine kinase inhibition altogether once they achieve a stable level of leukaemia remission. Most patients who achieve remission with tyrosine kinase inhibition are advised to continue taking the drug indefinitely, yet it is unclear whether continued therapy is necessary for all patients. Common side effects include cramps, fluid retention, excess fluid around the lungs, skin rashes, nausea, vomiting, diarrhoea, myocar- dial damage, and fatigue. Women are typically advised not to conceive while taking the drugs due to their high risk of birth defects.

low levels of leukaemia on very sensitive tests to safely try reducing their dose of tyrosine kinase inhibitor.

In the EUROpean leukaemia net Stop tKI (EURO-SKI) trial, one of the largest trials to assess the safety of stopping tyrosine kinase inhibition, about half of 821 patients with CML showed no evidence of relapse 2 years after treatment cessation, suggesting that a large number of patients can safely discon- tinue the drug. Study participants who had taken a TKI for more than 5.8 years before stopping were significantly less likely to experience relapse within the first 6 months (34.5% relapsed) versus those who had been on the therapy for a shorter duration (57.4%). Each additional year of tyrosine kinase inhibition increased a patient’s chances of successful discontinua- tion by about 16%. The study focused on patients with CML whose leukaemia was in deep remission. All participants had a stable, extremely low level of detectable leukaemia markers for at least 1 year before cessation of their TKI. After

PracticeUpdate Editorial Team

VOL. 2 • NO. 1 • 2017