Long-Term Follow-Up Shows Imatinib Discontinuation Remains Safe

After more than 6 years of follow-up, the STIM1 study shows that patients with chronic myeloid leukemia (CML) who have undetectable minimal residual disease (UMRD) can safely discontinue imatinib therapy. Though molecular recurrence (MR) can occur, restarting the therapy can still prevent disease progression.

“In addition to data suggesting that patients with deep molecular responses have a low risk of progression and a high rate of long-term survival, several ongoing discontinuation clinical trials have demonstrated that patients with sustained deep molecular responses can safely suspend TKI [tyrosine kinase inhibitor] therapy and achieve treatment-free remission,” wrote study authors led by François-Xavier Mahon, MD, PhD, of University Bordeaux in France. The STIM1 trial’s preliminary results previously showed that almost 40% of patients maintained a molecular remission after imatinib cessation.

The new analysis included all 100 patients in the trial, with a median follow-up of 77 months after imatinib discontinuation. All patients included had UMRD for at least 2 years prior to cessation. The results were published in the Journal of Clinical Oncology.

A total of 61 patients (61%) had confirmed MR during the follow-up period, most of which occurred within 6 months of imatinib cessation; the median time to MR was 2.5 months. One patient died with UMRD, at 10 months.

Most of the patients with confirmed MR (57 of 61) restarted therapy (imatinib in 56, dasatinib in 1) after a median of 2.1 months from MR. Three patients refused to resume therapy, and one was undergoing chemotherapy for a concomitant second neoplasm. Of those 57 patients, 55 achieved a second UMRD after a median of 4.3 months. None of the patients experienced CML progression during the study.

At the time of last follow-up, 57 patients were alive, and 43 of those (70%) were receiving TKI therapy. Nine of the 14 not on TKI therapy had achieved a sustained second UMRD and discontinued the treatment once again.

Among the 39 patients who never experienced an MR, 16 patients (41%) had a sustained UMRD, and the other 23 had intermittent positive BCR-ABL:ABL IS ratio; none of those patients, however, experienced loss of major molecular response, or MR according to the study’s definition.

On a multivariate analysis, Sokal risk score and duration of imatinib therapy were significantly predictive of MR. Patients with low or intermediate Sokal score and an imatinib duration of longer than 54 months had a lower risk of MR compared with the other patients in the study.

“We hypothesize that a careful selection of patients on the basis of a sustained deep molecular response before imatinib may partially explain the success of imatinib discontinuation,” the authors wrote. “Whether patients who do not achieve such sustained deep molecular response are not good candidates for imatinib discontinuation remains debatable.”