Report on EHA 2014 – Part 3
European Hematology Association annual meeting, Milan, Italy, June 12-15, 2014
The advent of more potent TKIs, such as Sprycel and Tasigna, and the use of these agents earlier on has enabled many people to achieve a faster and deeper molecular response. A deep molecular response is defined as a 4.5-log reduction in BCR-ABL transcripts, which means that CML is essentially undetectable. Undetectable doesn’t necessarily mean cured, but it does raise the possibility that some people may be able to remain free of detectable disease even after they stop taking their medication. The risk, of course, is that stopping treatment may allow CML to re-emerge and re-gaining control may become more difficult.
One of the first studies to investigate this idea of going off treatment was the Stop Imatinib (STIM) trial (Mahon and colleagues. Lancet Oncol 2010;11:1029-1035). It found that 41% of people with a complete molecular response (CMR) were able to maintain CMR while off treatment for a year.
Three new Stop trials were presented at EHA 2014. In the EURO-SKI trial, candidates for stopping treatment were selected if they had achieved a 4-log reduction or better in BCR-ABL transcripts and had maintained that level of control for at least a year (Saussele and colleagues. EHA 2014; abstract LB-2440). Thus far, among the first 200 people who stopped treatment, 62% maintained good control of their CML after six months. The study is ongoing.
Similar results were seen in a report that primarily included people from the Korean Imatinib Discontinuation Study (KIDS) trial (Oh and colleagues. EHA 2014; abstract P290). A total of 94 people participated. The median age was 48 years; the median time on a TKI before stopping was 6-7 years (a median of 3-4 years with undetectable CML). One year after stopping, 65% continued to have undetectable disease. All of those who developed detectable disease were able to re-gain control after starting treatment again. Interestingly, people who stopped treatment didn’t find that they felt physically or mentally better (Park et al. EHA 2014; abstract P291). However, younger women had the greatest boost to physical and mental well-being after stopping treatment.
In the DADI discontinuation trial of Sprycel, 64 people with CMR for at least a year while on treatment with Sprycel tried stopping therapy (Kimura and colleagues. EHA 2014; abstract P289). All had previously been treated with Gleevec or another treatment before switching to Sprycel. Overall, 30 of 62 people completing six months off treatment, meaning that 48% remained free of detectable disease. For those who lost CMR, 97% re-attained CMR within three months of re-starting Sprycel.
The conclusion of all of these studies is that a significant proportion of people who achieve a deep molecular response can stop treatment and stay off treatment for up to a year. For those who lose their molecular response, their CML appears to remain sensitive to treatment and re-starting therapy allows them to re-gain control of their disease.
Bosulif (bosutinib) is the most recently approved TKI (in some countries), but its use is generally limited to people who haven’t responded to Gleevec and/or Tasigna or Sprycel. A small study in Spain has looked at how well Bosulif worked in people who hadn’t responded to three prior TKIs (Garcia-Gutierrez and colleagues. EHA 2014; abstract P902). A total of 1 in 4 people with a previously poor response were able to achieve a complete cytogenetic response, and 16% achieved a major molecular response. In the group with some degree of response to prior therapy, most either maintained that response or showed improvement after switching to Bosulif. Treatment was well tolerated. The most common side effects were gastrointestinal (diarrhea, nausea, stomach pain) and rash.
A novel TKI, radotinib, is available in Korea as a treatment option in people who don’t do well on Gleevec. A phase II study of 77 people reported that 70% achieved a complete cytogenetic response by two years; 46% had a major molecular response (Kim and colleagues. EHA 2014; abstract P284; published as Kim and colleagues. Haematologica 2014;99:1191-1196). However, most people stopped taking the drug within the first two years.