番茄社区

SAN DIEGO -- Patients with stable chronic myeloid leukemia (CML) might be able to stop taking their medications or at least reduce the dose safely in many cases, researchers reported here.

But eliminating or reducing the dose of tyrosine kinase inhibitors (TKIs) -- the backbone of CML therapy -- increases the risk of relapse after years of stable disease, the investigators told reporters at the annual meeting of the American Society of Hematology (ASH) annual meeting.

An "emerging goal" of doctors managing patients with CML is to stop treatment, but it's not yet clear what preconditions allow halting therapy safely, according to , of Bergonie Cancer Center at the University of Bordeaux in France.

His group analyzed outcomes for 755 patients who stopped treatment after at least 3 years on a TKI and at least a year with a deep molecular response of MR4.

Meanwhile, researchers led by of the Institute of Cancer Sciences at University of Glasgow in Scotland, conducted a similar study of 174 patients who cut their TKI dose by half.

In both studies, a proportion of patients relapsed, although the rate was higher when the TKIs were stopped entirely, leading an outside expert to comment that it's "still an open question" whether either practice should become routine.

"Keep in mind that (the development of TKIs for CML) is the single greatest success story we have in cancer therapy in 4 decades," said , of the Cleveland Clinic's Taussig Cancer Institute, who was not part of the studies, but who moderated an ASH media briefing.

"These drugs changed the face of how these patients were treated," he told 番茄社区, to the point that bone marrow transplants, once the standard of care in CML, are now rare.

Sekeres said he was somewhat reassured by the findings from Copland's group that only 12 of the 174 patients relapsed. But to some extent, "they spiked their punch" by choosing mostly patients with deep molecular remissions -- 49 patients had MR3 responses at study entry but 125 had MR4 responses, he added.

Nine of the relapses occurred in the MR3 patients and just three among those with MR4 responses, Copland reported.

Mahon's group also chose patients with deep molecular responses, but they saw a relapse rate of 50% after 2 years without TKIs. "I'm less reassured" by those results, Sekeres said.

One of the factors driving the desire to reduce or eliminate drug therapy for CML is the . Sekeres said he has patients who have reduced their dose themselves because they are unable to pay for the medications, although he has not made a clinical decision to do that.

Indeed, the DESTINY study found that dose reductions led to a 46.7% drop in the expected cost of TKIs for the patients in the trial, Copland said. She added that TKI-related symptoms improve over the first 1 or 2 months with lower doses, but then become stable.

In the EURO-SKI trial, Mahon's group concluded that stopping therapy in about half of patients was both "feasible and safe," although 373 of the 755 assessable patients had relapsed and four had died in remission.

The only factor that appeared to predict longer drug-free remissions was long-term therapy of at least 5.8 years with the TKI imatinib (Gleevec).