It’s still a coin toss – a 50/50 chance of chronic myeloid leukaemia (CML) patients with deep molecular response on tyrosine kinase inhibitors (TKi) maintaining treatment-free remission if they stop treatment.
And while some patients are keen to stop at the earliest possible opportunity, others can be reassured that there is minimal risk with continuing on the medications.
Speaking at Blood 2018, haematologist Dr David Ross from SA Pathology said he recommended at least two years with deep molecular response (MR4.5) of at least two years before stopping treatment.
He said the updated ENESTfreedom study found almost half (48.9%) of patients previously treated with nilotinib remained in treatment-free remission at 96 weeks.
Deeper molecular response at 12 weeks of treatment-free remission appeared to predict sustained remission at 96 weeks.
Reassuringly, the study also found most of the patients who reinitiated treatment regained their molecular response promptly.
Dr Ross said that all the evidence points to deeper levels of response being better for patients attempting to achieve treatment-free remission.
“If someone has been on imatinib for eight years in deep molecular response, I might tell that patient their chances [of staying in remission] are more like 60/40 but it’s not like 80/20 and that is really want people want I think – to have a clearer difference in outcome,” he told the limbic.
He said the CML8 study of patients in long-term treatment-free remission following imatinib found a slow decay in the level of residual leukaemia cells using highly sensitive BCR-ABL1 DNA PCR testing.
The findings supported an earlier study, also following imatinib, in which digital PCR could help predict relapse.
“Age is also reported in that study but not shown consistently in other studies… certainly the digital PCR has been shown in that one study to be associated. And our own study, while the numbers are small, was not significant but the same trend was seen.”
Dr Ross said patients going off treatment should be warned about TKi withdrawal syndrome, which had an incidence of about 30-40% and was more likely to affect women.
Onset was typically within three to six weeks after stopping treatment, with some patients requiring corticosteroid treatment.
“So I do warn people about that because you can imagine if someone has felt perfectly well on their drug suddenly starts aching all over, they are going to panic and think something terrible is happening so I think it’s very important they are aware of that before they stop.”
Dr Ross said the long relationship with patients before they would qualify to stop treatment provided ample time to ‘drip feed information and answer questions’ about the risks, benefits and possibilities of treatment- free remission.
“We’re looking after these patients for years before these questions arise. So if someone has achieved a deep molecular response, I am going to have that patient on treatment for two years – time to have this conversation.”
“So when the time comes it’s not a shock to the patient. He or she has had time to think about it and most patients have already decided. Some even book their appointment to see me on the 2-year anniversary of achieving a deep molecular response because they have decided that on that day they will stop.”
He said he continues with monthly testing for the first six months after stopping treatment but because relapse was unlikely within the first 3-4 months it was not necessary to see patients unless they required management of TKi withdrawal syndrome.