Long-term follow-up of the French 1 Stop Imatinib Study (STIM1) in patients with chronic myeloid leukemia (CML) has demonstrated that imatinib (Gleevec) can be safely discontinued in patients with a deep molecular response (ie, lasting at least 2 years). According to data presented at ASH 2015, molecular relapse was very rare after 6 months of stopping imatinib, and no relapse was reported after 2 years.
“With a median follow-up greater than 5 years after stopping treatment, no CML event progression has been reported,” said Gabriel Etienne, MD, PhD, Institut Bergonié, Bordeaux, France, “and most, if not all, relapsing patients have achieved a second deep molecular response after resumption of tyrosine kinase inhibitors.”
“Imatinib discontinuation is safe, provided that a deep sustained molecular response has been achieved before discontinuation and close molecular monitoring is available after treatment cessation,” Dr Etienne added.
In the multicenter STIM1 study, imatinib given for more than 3 years was prospectively discontinued in 100 patients with CML (48 male, 52 female) who were in deep molecular response with undetectable minimal residual disease sustained for at least 2 years. The median follow-up after treatment discontinuation was 65 months.
Overall, 61 patients had molecular relapse, and 4 patients died of causes unrelated to their CML after relapse. At only 2.5 months, the median time to molecular relapse was very short, said Dr Etienne, with 80% of relapses occurring between months 1 and 3 after discontinuation.
After relapse, 57 of 61 patients restarted treatment, and 55 patients achieved a second complete molecular response, with a median time of 4.2 months after resuming treatment.
The median time from molecular relapse to treatment resumption was only 2.1 months, Dr Etienne reported.
“At the median follow-up of 65 months, none of the molecular relapse patients have CML progression,” said Dr Etienne, who noted that treatment resumption in patients who relapsed was associated with the achievement of a second undetectable minimal residual disease in almost all patients.
The second objective of the analysis was to identify factors associated with molecular relapse. According to Dr Etienne, only the Sokal risk score was significantly associated with molecular relapse.
“Sokal risk score continues to be a strong significant factor associated with molecular relapse, suggesting that eradication of the leukemic clone may depend on intrinsic features of the disease,” he said.
“We have to keep in mind that half of the patients have been previously treated with interferon alpha, which may limit the statistical analysis of predictive factors,” Dr Etienne concluded.