Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase III, Randomized, Open-label, Multi-center FESTnd Study

Abstract

Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome–positive chronic myeloid leukemia (CML-CP). Patients and Methods: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups. Results: The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm. Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644. See related commentary by Müller, p. 3

Interferon-α may help prevent molecular relapse of chronic myeloid leukemia after the discontinuation of tyrosine kinase inhibitors

“…of imatinib (bordy surface area (BSA) = 1.3 m 2 ), and reached MMR and MR 4.5 after 12 and 18 months of imatinib treatment, respectively. Patient 2 received second-generation TKI flumatinib (China’s original research second-generation TKI) 24 as first-line treatment, and reached MR 4.5 after 6 months of flumatinib treatment. The Sokal score was calculated for 40 patients (missing data prevented Sokal score calculation for the other nine patients); 26 were classified as low-risk, 12 as intermediate-risk, and two as high-risk.…”

A Unique Three-Way Variant Philadelphia Chromosome t(6;9;22)(p21.3;q34;q11.2) in a Newly Diagnosed Patient with Chronic Myeloid Leukemia Responded to Flumatinib

“…No patients had progression to accelerated phase or blast crisis in the flumatinib group vs 4 patients in the imatinib group by 12 months. 18 Whether flumatinib is effective in CML patients with vPh chromosomes has not been reported in the literature.…”

A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase

“…In addition, there are other potential agents for patients who experience treatment failure or intolerance to dasatinib, nilotinib, or bosutinib (Table 3 ). These include the 2G TKIs radotinib and flumatinib, both of which have shown improved efficacy over imatinib in ND CML-CP in phase 3 clinical trials with tolerable safety profiles [ 95 , 96 ], and are being assessed as potential 2L options in patients with CML-CP resistant or intolerant to 1L therapy; the third-generation TKIs vodobatinib and olverembatinib [ 97 – 100 ]; and PF-114, a potent TKI that has demonstrated efficacy in a phase 1 trial in patients with CML-CP who have previously been treated with at least two therapies or patients with the T315I mutation who have been treated for ≥ 6 months [ 101 ]. The continued emergence of new therapies is welcomed and will change the way clinicians treat CML in the future.…”

“… Data not yet available. Flumatinib : imatinib derivative that displays increased efficacy over imatinib in Chinese patients with ND CML-CP with a similar safety profile [ 96 ] FESTnd (NCT02204644) [ 96 ]: phase 3 trial: flumatinib vs. imatinib in ND CML-CP MMR at 6 months (primary endpoint): Flumatinib 34%, imatinib 18% ( P = 0.0006) EMR at 3 months (secondary endpoint): Flumatinib 82%, imatinib 53% ( P < 0.0001) All-grade AEs more frequent in flumatinib arm: Diarrhea ( n = 79/196, 40%) Alanine transaminase elevation ( n = 51/196, 26%) All-grade AEs more frequent in imatinib arm: Edema ( n = 70/198, 35%) Pain in extremities ( n = 49/198, 25%) Rash ( n = 28/198, 14%) Neutropenia Thrombocytopenia Anemia Hypophosphatemia NCT04677439: currently recruiting patients to a phase 4 trial in China: efficacy and safety of flumatinib in patients with Ph + CML-CP post-imatinib failure Data not yet available. Data not yet available.…”