Flumatinib for the Treatment of Adult Patients with Resistant or Intolerant Chronic-Phase Chronic Myeloid Leukemia: Results from Real-World Data

Introduction Over the past decades, BCR-ABL1 tyrosine kinase inhibitors (TKIs) as the initial treatment for chronic phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML-CP) have dramatically turned CML-CP into a manageable and potentially curable chronic disease. Nonetheless, in spite of the massive improvement in CML treatment over the last years with the introduction of TKIs, some patients (20%-30%) display intrinsic or acquired resistance to treatment during the disease course. Flumatinib Mesylate is a newer and orally available TKI with higher selectivity and potency against BCR-ABL1 kinase versus imatinib. According to the previous data，flumatinib can be an effective first-line treatment for CML-CP.

Patients and Methods This study was initiated mainly to observe the safety and efficacy of flumatinib in the treatment of adult patients with resistant or intolerant Chronic-Phase Chronic Myeloid Leukemia, especially in second-line or above treatment in the real world. Efficacy and safety assessments were collected for the intent-to-treat population. Major molecular response (MMR) was defined as BCR-ABL1 transcript level ≤ 0.1% on the International Scale (IS), molecular response (MR4) was defined as BCR-ABL1 transcript level (IS) ≤ 0.01%; MR4.5 was defined as a BCR-ABL1 (IS) transcript level ≤ 0.0032%. DMR was defined as MR 4.0 or MR 4.5.

Results Among the 58 evaluable patients with CML-CP, 54% were male, 47% were female. The median age of these patients is 45Y. During the observation period, there were 28 second-line conversion patients (48%), 19 third-line conversion patients (33%), and 11 fourth-line and above patients (19%). Prior therapies included imatinib, dasatinib, nilotinib, olverembatinib, radotinib and ponatinib. All patients converted to treatment of 600mg flumatinib daily. Among the 58 evaluable patients, 20 patients who had been treated with imatinib alone were converted to flumatinib, including 9 cases of IM resistance, 8 cases of IM intolerance and 2 case of personal reasons. During the 1-year follow-up, 52% of patients (n=30) were evaluable for the achievement of MMR. The patients with BCR-ABL1 (IS) > 10% at baseline, 3, 6 and 12 months were 48%, 17%, 23% and 26%, respectively; for patients with BCR-ABL1 (IS) < 0.1% were 26%, 40%, 49% and 52%, respectively; for patients with DMR were 26%, 40%, 49% and 52%, respectively. For imatinib-intolerant or -resistant patients, MMR was 44%. Subgroup analyses showed that the imatinib-intolerant or -resistant patients with BCR-ABL1 (IS) >10% at baseline, 3, 6 and 12 months were 65%, 0%, 10% and 0%, respectively; for patients with BCR-ABL1 (IS) < 0.1% were 10%, 33%, 80% and 44%, respectively; for patients with DMR were 5%, 11%, 30% and 11%, respectively. Meanwhile, 11% of patients could not be detected at molecular level (0.000%). Of the 58 patients, only Grade 1 AEs were reported, including diarrhea, rash and eye edema.

Conclusion Flumatinib has good efficacy and safety in the treatment of adult patients with resistant or intolerant Chronic-Phase Chronic Myeloid Leukemia, it will be a good choice for second-line or above treatment for CML-CP In clinical practice.