Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia

Abstract

Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up. Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point. Results The median molecular follow-up after treatment discontinuation was 77 months (range, 9 to 95 months). Sixty-one patients lost UMRD after a median of 2.5 months (range, 1 to 22 months), and one patient died with UMRD at 10 months. Molecular recurrence-free survival was 43% (95% CI, 33% to 52%) at 6 months and 38% (95% CI, 29% to 47%) at 60 months. Treatment was restarted in 57 of 61 patients with MR, and 55 patients achieved a second UMRD with a median time of 4 months (range, 1 to 16 months). None of the patients experienced a CML progression. Analyses of the characteristics of the study population identified that the Sokal risk score and duration of IM treatment were significantly associated with the probability of MR. Conclusion With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.

Rationale and motivating factors for treatment-free remission in chronic myeloid leukemia

“…At present, available evidence shows that most molecular relapses occurred within 6 months of TKI discontinuation. [7,9,13,14,17] With 65 months' In a previous analysis from KIDS, longer durations of imatinib therapy and UMRD prior to suspension of imatinib were associated with increased probability of sustained MMR. [94] i Data from EURO-SKI are from a preplanned interim analysis of the first 200 patients with a 6-month assessment.…”

“…[9] In STIM1, 57 of the 61 patients with molecular relapse reinitiated TKI therapy, and 55 regained UMRD. [17] All patients in TWISTER who experienced molecular relapse (n ¼ 22) had 1 UMRD sample with imatinib retreatment, with a median time of 3 months to achieve UMRD. [7] In A-STIM, all 31 patients who reinitiated treatment following loss of MMR regained the response, and 23 regained UMRD.…”

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17] In reports of patients who stopped imatinib without achieving deep molecular responses, rapid relapses requiring treatment reinitiation were typical. [56,57] In addition to achievement of deep molecular responses, other potential predictors of TFR success have been assessed in a number of TFR studies (Table 2).…”

“…In the Stop Imatinib 1 (STIM1) trial, patients with low Sokal risk had a higher probability of successful TFR than those with high Sokal risk. [17] In the Stop Second-Generation TKI (STOP 2G-TKI) and Dasatinib Discontinuation (DADI) trials, a history of imatinib resistance or suboptimal response was associated with a lower rate of TFR. [13,14] These results suggest that patients with a more aggressive CML biology may be less likely to maintain TFR.…”

“…[2] However, there is increasing evidence demonstrating that, within the context of a clinical trial and with rigorous molecular monitoring, some patients may be able to suspend TKI therapy without losing their responses, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] a state known as treatment-free remission (TFR).…”