Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study

Abstract

Key Points• First-line or subsequent dasatinib or nilotinib can be safely stopped in CML patients with deep and longlasting molecular responses. • A suboptimal response or resistance prior to dasatinib or nilotinib is associated with significantly worse treatmentfree remission.STOP second generation (2G)-tyrosine kinase inhibitor (TKI) is a multicenter observational study designed to evaluate 2G-TKI discontinuation in chronic myeloid leukemia (CML). Patients receiving first-line or subsequent dasatinib or nilotinib who stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the 2 preceding years at least were eligible for inclusion. This interim analysis reports outcomes of 60 patients with a minimum follow-up of 12 months (median 47, range: 12-65). Twenty-six patients (43.3%) experienced a molecular relapse defined as the loss of a major molecular response (MMR). Relapses occurred after a median time of 4 months (range: 1-38). Cumulative incidences of molecular relapse by 12 and 48 months were 35% (95% confidence interval [CI], 24.79% to 49.41%) and 44.76% (95% CI, 33.35% to 59.91%), respectively. Treatment-free remission (TFR) rates at 12 and 48 months were 63.33% (95% CI, 51.14% to 75.53%) and 53.57% (95% CI, 40.49% to 66.65%), respectively. In univariate analysis, prior suboptimal response or TKI resistance was the only baseline factor associated with significantly worse outcome. A landmark analysis demonstrated that loss of MR4.5 3 months after stopping TKI was predictive of failure to maintain MMR later on. During the treatment-free phase, no progression toward advanced phase CML occurred, and all relapsing patients regained MMR and MR4.5 after restarting therapy. In conclusion, discontinuation of first-line or subsequent 2G-TKI yields promising TFR rates without safety concerns. Further research is encouraged to better define conditions that will offer patients the highest chance to remain free from 2G-TKI therapy. (Blood. 2017;129(7):846-854)

Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

“…Regular molecular monitoring has been incorporated into several CML treatment guidelines produced since 2006 and updated over time [1][2][3][4][5]. Disease monitoring and assessment of response have led to the design of therapeutic algorithms for adult CML, including treatment discontinuation strategies for patients with a deep and sustained molecular response (MR) [6][7][8][9]. As a result, the overall prognosis has changed dramatically, and the use of allogeneic hematopoietic stem cell transplantation (HSCT) in adults with CML is now limited to selected patients.…”

Long-Term Outcomes of Tyrosine Kinase Inhibitors Treatment for Chronic Myeloid Leukemia

“…This increase in efficacy must be associated with the disadvantage of the adverse effects of this protein and the consequent decrease in quality of life. The elective suspension has also been orchestrated with second generation TKIs (nilotinib and dasatinib), with results similar to those of imatinib [31]. After interrupting the TKI, it is necessary to frequently monitor PCR every three months (first year) and every six months afterward, until loss of response.…”

Chronic Myeloid Leukemia—the Promise of Tyrosine Kinase Inhibitor Discontinuation

“…The first study report was by Rea et al[39]. In that Stop 2G-TKI study patients with CP-CML/AP-CML at diagnosis, receiving 1st or subsequent line dasatinib or nilotinib at any dose were enrolled.…”