Flumatinib, a second-generation tyrosine kinase inhibitor (TKI), led to more molecular responses that were also deeper, compared with imatinib, in patients with newly diagnosed Philadelphia chromosome–positive, chronic-phase chronic myeloid leukemia (CP-CML), according to results of a phase III study presented at the 2019 American Society of Clinical Oncology (ASCO) annual meeting. The investigational BCR-ABL1 TKI also had a similar safety profile to imatinib.
These findings support flumatinib as a frontline treatment option for patients with newly diagnosed CP-CML, the investigators, led by Zhang Li, MD, from State Key Laboratory of Experimental Hematology of the Chinese Academy of Medical Sciences in Tianjin, reported. Co-author Bingcheng Liu, MD, presented the results.
This open-label phase III study included 400 patients with previously untreated CP-CML recruited from 25 centers across China. Participants were stratified by Sokal score and randomized 1:1 to receive flumatinib 600 mg/day or imatinib 400 mg/day. As of the data presentation, 393 patients were evaluable for response: 196 in the flumatinib group and 197 in the imatinib group. Baseline characteristics were similar between the groups: Median age was 45 years in each arm, and similar proportions of patients in each group had intermediate risk disease (68% in the flumatinib arm and 67% in the imatinib arm, per Sokal risk group).
For the study’s primary endpoint, investigators assessed major molecular response (MMR; defined as BCR-ABL ≤0.1%) at six months; molecular response was assessed at a central laboratory that was blinded to treatment allocations during the study.
At last follow-up, 159 patients in each arm (81%) were still receiving study treatment. The most common reasons for discontinuation were drug-related adverse events (AEs; 20 patients in the flumatinib arm and 12 patients in the imatinib arm). One flumatinib-treated patient died during follow-up.
Compared with patients in the imatinib group, more patients in the flumatinib group experienced an MMR at six, nine, and 12 months:
- 6 months: 35.2% vs. 19.3% (p=0.0002)
- 9 months: 49.7% vs. 32.2% (p=0.001)
- 12 months: 57.2% vs. 39.2% (p=0.001)
Flumatinib appeared to be associated with early induction of molecular responses, Dr. Li added, with higher rates of early molecular response at three months, regardless of BCR-ABL level:
- BCR-ABL≤10%: 83.4% vs. 54.4% (p<0.001)
- BCR-ABL ≤1%: 42.5% vs. 13% (p<0.001)
- BCR-ABL ≤0.1%: 8.3% vs. 2.1% (p=0.006)
“More patients in the imatinib group experienced disease progression to accelerated phase or blast crisis,” she reported, with four progressions in the imatinib group, compared with none in the flumatinib group (p=0.04).
The second-generation TKI also appeared to have a similar safety profile to imatinib, with comparable rates of grade 3/4 treatment-emergent AEs. Nonhematologic AEs generally were higher in the imatinib-treated group, except for diarrhea. Hematologic AEs also were more common in the imatinib than the flumatinib group (neutropenia: 60% and 31%; anemia: 29% and 16%; p values for comparisons not provided). Overall, though, Dr. Li reported that “there were no AEs specific to second- and third-generation TKIs observed.”
Although the study met its primary endpoint, with a comparable safety profile and a superior efficacy profile to imatinib at all timepoints, the findings are limited by its open-label design, which could have potentially introduced bias.
The authors report no relevant conflicts of interest.
Li Z, Meng L, Zhang Y, et al. Frontline flumatinib versus imatinib in patients with chronic myeloid leukemia in chronic phase: Results from the China randomized phase III study. Abstract #7004. Presented at the 2019 ASCO Annual Meeting, June 1, 2019; Chicago, IL.