Drugs known as tyrosine kinase inhibitors (TKI), including imatinib, nilotinib, and dasatinib, are so effective at controlling chronic myeloid leukaemia (CML) that some patients seek to avoid the drugs’ side effects and save costs by reducing the TKI dose or discontinuing TKI treatment altogether once they have achieved a stable level of leukaemia remission.

Thanks to these drugs, the life expectancy of patients with CML now approaches the life expectancy of the general population.

Although the drugs are highly effective at keeping leukaemia in check, their side effects and cost have led some patients and their doctors to question whether it would be feasible to discontinue their use after a patient achieves consistently negative leukaemia test results.

Under current guidelines, most patients who achieve remission with TKI therapy are advised to continue taking the drugs 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, damage to the heart, and fatigue, and women are typically advised not to conceive children while taking the drugs due to the high risk of birth defects.

Two presentations at ASH 2016 show safety, and even beneficial outcomes for some patients who stop TKI treatment.

In the first, one of the largest ever trials to assess the safety of stopping TKI therapy, about half of 821 CML patients showed no evidence of relapse two years after treatment cessation, suggesting that a large number of patients can safely discontinue TKI use.

Francois-Xavier Mahon, MD, PhD, Bergonie Cancer Center, University of Bordeaux, France, will present this study during an oral presentation on Monday, December 5, at 10:30 a.m. PST in Pacific Ballroom 18–19 of the Marriott Marquis San Diego.

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 six months (relapse occurred in 34.5% of these patients) compared to those who had been on the therapy for a shorter duration (57.4%), according to the research team.

Each additional year of TKI therapy increased a patient’s chances of successful TKI discontinuation by about 16 percent.

The study focused on CML patients whose leukaemia was in deep remission.

All participants had a stable, extremely low level of detectable leukaemia markers for at least one year before TKI cessation.

After stopping TKI therapy, 62 percent showed no evidence of leukaemia recurrence at 6 months, and half (52%) showed no recurrence at 24 months.

Of the patients who experienced molecular recurrence, most regained their previous remission level after resuming TKI therapy, and no study participants progressed to a dangerous state of advanced disease.

This study was supported by European Leukaemia Net (ELN) and was partially funded by the French National Institute of Cancer (INCA).

In the second study, led by researchers at the University of Liverpool, United Kingdom, analysis suggests many CML patients may be able to safely reduce TKI side effects by cutting their dose in half.

Mhairi Copland, MD, PhD, University of Glasgow, United Kingdom, will present this study during an oral presentation on Monday, December 5, at 3:00 p.m. in Pacific Ballroom 18–19 of the Marriott Marquis San Diego.

In contrast to other trials, which focus on patients who are nearly free of leukaemia as measured by very sensitive tests, the new Destiny study included some patients with a stable molecular remission level demarcated according to international standards as MR3 — a level the researchers describe as “good, but not perfect.”

The results suggest that a wider range of patients may be able to safely reduce TKI therapy than was previously thought feasible.

Of 174 study participants, the vast majority (93%) showed no evidence of leukaemia rebound one year after cutting their TKI dose, and many reported a significant decrease in TKI-associated side effects within the first three months.

Just 12 participants showed signs of leukaemia recurrence, all of whom regained a remission level of MR3 or better within four months of resuming a full TKI dose.

“Taken together, these findings might indicate that some patients are being unnecessarily over-treated,” said study author Mhairi Copland, MD, PhD of the Institute of Cancer Sciences, University of Glasgow, United Kingdom. “The other important implication is that patients do not have to have extremely low levels of leukaemia on very sensitive tests in order to safely try reducing their TKI dose.”

Participants who started with extremely low levels of leukaemia (MR4) were significantly less likely to experience a leukaemia rebound (seen in 2.4% of these patients) compared with those classified as MR3 (18.4%), but Copland said the low rates of rebound overall suggest it is safe for MR3 patients to attempt to reduce their TKI dose if desired.

Any benefits in terms of reducing side effects should become apparent within the first three months.

Source: ASH 2016