Recently, the 65th ASH Annual Meeting and Exposition announced the papers and reports to be represented at this year's event, among which four study results on Hansoh Pharma's novel drug flumatinib were successfully selected, enabling flumatinib to further build its reputation as a first second-generation TKI drug independently developed in China at the premier international hematology conference. This drug has also provided an opportunity to continue to explore and provide  more therapeutic options for patients in China and around the world.

The 65th ASH Annual Meeting and Exposition will take place from December 9 to 12, 2023 in San Diego, U.S.A. It is the world's most large-scale comprehensive hematology event, with programs covering both malignant and non-malignant hematological diseases. More than 25,000 hematologists and relevant healthcare professionals from over 100 countries around the globe are expected to attend the meeting and share the most cutting-edge advances and groundbreaking clinical data in hematology.

Flumatinib, China's first self-developed second-generation TKI drug, was approved for market release in November 2019, and then was recommended as a first-line treatment for CML-CP in the "Guidelines for Diagnosis and Treatment of Chronic Myelogenous Leukemia in China (2020 edition)". The drug is now widely used in clinical practice. Four flumatinib studies were successfully selected by this year's ASH Annual Meeting and Exposition, for which the details are as follows.

1. Flumatinib Versus Nilotinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

First author：Suning Chen，The First Affiliated Hospital of Soochow University, Jiangsu Province, China

Corresponding author：Depei Wu,The First Affiliated Hospital of Soochow University, Jiangsu Province, China

Introduction: Tyrosine kinase inhibitors (TKIs) have considerably improved the long-term clinical outcomes in patients with chronic phase chronic myeloid leukemia (CML-CP). Most of these patients receive 1st generation TKI imatinib as first-line therapy; however, an increasing number of patients are now receiving 2nd generation TKIs as first-line therapy, because of the more potent BCR-ABL1 inhibition with proven efficacy in patients resistant or intolerant to imatinib. Flumatinib is a novel 2nd generation BCR-ABL1 TKI with promising efficacy and manageable safety in newly diagnosed CML-CP. Compared to imatinib, significantly higher rates of 12-month major molecular response (MMR) and complete cytogenetic response were observed in patients with CML-CP, and also a shorter time to achieve these responses. Though there have been many studies comparing 2nd generation TKIs vs imatinib in CML-CP, studies comparing clinical outcomes between different 2nd generation TKIs are scarce. Here, we report the real-world effectiveness and safety of flumatinib and nilotinib in patients with newly diagnosed CML-CP. A total of 446 patients were enrolled in the study since November 2020 to August 2022, and 150 in nilotinib, 296 in flumatinib groups, respectively. The baseline characteristics of the two groups were comparable.

Results: No significant difference in the rate of MMR was observed at 12 months between nilotinib and flumatinib (78% vs 80%; P=0.68). Similarly, no significant difference was observed in the rate of EMR at 3 months (85% vs 89%; P=0.26) and the rate of optimal molecular response at 6 months (93% vs 92%; P=0.70; BCR-ABL1 is ≤1%) between the two groups. The overall safety profile was similar either, hyperbilirubinemia (47% vs 7%), increased ALT (33% vs 12%), increased AST (24% vs 9%), rash (30% vs 18%) and anemia (19% vs 10%) were more frequent in nilotinib than flumatinib, whereas diarrhea was lower in nilotinib than flumatinib (2.7% vs 8.8%). The incidence of grade 3-4 AEs were reported 13% in nilotinib and 10% in flumatinib. The safety of flumatinib was more favorable if compared to that of nilotinib, such as hepatic and skin toxicities etc.

2.  Evaluating Effectiveness and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia in (CML-CP) without Optimal Response (Warning, Failure) to Imatinib or/and Dasatinib

First author：Weiming Li，Department of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Corresponding author：Yu Hu, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Introduction: This prospective, multicentre study enrolled Philadelphia Chromosome-Positive (Ph+) CML-CP patients aged ≥18 years and who failed to achieve the optimal response with imatinib or/and dasatinib between March 2021 to October 2022. All patients were treated with flumatinib 600 mg once a day and followed up to 24 months.

Results: Overall, 94 patients with Ph+ CML-CP were included in the study. The median (range) age of the patients were 53 (19.0-84.0) years old and 61.7% of the patients were males. A total of 38 (40.4%) patients reported warning response from the previous TKIs whereas 56 (59.6%) of patients reported treatment failure to the previous TKIs. Seventy-seven (81.9%) patients have been treated with one TKI, either imatinib or dasatinib, and 17 (18.1%) have been treated with both prior to the study. Overall, 25 (54%) patients achieved MMR at 12-months follow-up compared to the baseline (Figure 1). The rates of optimal molecular response at 3- and 6-months were also improved compared to the baseline. The optimal molecular response was 76(88%) at 3 months, and 52(73%) at 6 months. Subgroup analysis with previous response to TKIs revealed that flumatinib improved the rates of optimal molecular response in both warning and failure groups. Switching to flumatinib from imatinibor/and dasatinib have been reported with an enhanced optimal molecular response in patients who experienced warning compared with those who had treatment failure after the TKIs with 38 (100%) vs 38 (79%), 29 (91%) vs 23 (59%) and 15 (68%) vs10 (42%) at 3-, 6- and 12-months respectively (Figure 2). Similarly, the rates of optimal molecular response were improved inpatients without mutations compared to those having mutations, 65 (90%) vs 9 (75%) at 3 months, 46 (77%) vs 5 (56%) at 6months and 23 (59%) vs 1 (20%) at 12 months respectively. The most common adverse events (AEs) were diarrhea in 17 (18%), rash in 11 (12%), bloating in 11 (12%), and thrombocytopenia in 11 (12%) patients. Common hematological AEs of grade 3/4 were thrombocytopenia in 7 (7%), anemia in 3 (3%) and leucopenia in 1 (1%) patients. For Ph+ CML-CP patients without the optimal molecular response in previous imatinib or/and dasatinib, flumatinib is a better alternative to the existing treatments. In addition, if the patients were switched to flumatinib earlier, the optimal response was achieved faster.

3. Flumatinib for newly diagnosed Chronic Phase Chronic Myeloid Leukemia: An Open-Label, Multi-Center Study

First author：Na Xu, Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Corresponding author：Xiaoli Liu, Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Introduction:Tyrosine kinase inhibitors (TKIs) ushered in the era of targeted therapy for chronic myeloid leukemia (CML), which greatly improved the prognosis of patients with CML. Flumatinib is a second-generation tyrosine kinase inhibitor (TKI), which is currently approved for patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in China. And some current clinical trials revealed that flumatinib has been shown to be a more potent inhibitor of BCR::ABL than imatinib.

Results: From October 2020 to December 2022, a total of 158 patients with CP-CML were assessed for eligibility, of whom 127 were followed up for more than 3 months. 79(62%) patients were men and 48 (38%) were women. The median age was 47 years (range, 19-82 years), the median time from diagnosis to treatment was 6 days (0-176 days) and the median follow-up was 9.7 months (range 3.1-26.6 months). Of evaluable 127 patients, EMR was achieved by 85% (95% confidence interval [CI], 77.6%-90.7%) of patients at 3 months. After the initiation of flumatinib treatment, the incidence of MMR at 3, 6, and 12 months was 24%, 59%, and 73%, respectively. Patients receiving flumatinib had higher rates of CCyR at 6 months and MMR 12 months than the data from DASISION (dasatinib) and ENESTnd (nilotinib) therapy (85% vs 73% vs 67% and 73% vs 46% vs 44%). Progression-free survival (PFS) rate at 1-year was 97.2%. Diarrhea (34%) were the most commonly reported adverse events. Most treatment-related adverse events were grade 1/2. None of the patients discontinued or died due to AEs.

4. Real-World Safety and Clinical Response of Flumatinib in the Treatment of Chronic Myeloid Leukemia: A Retrospective Study

First/ Corresponding author：Chunyan Chen, Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China

Introduction: A total of 61 patients who received flumatinib as first-line therapy were compared with 92 patients who received first-line imatinib therapy. Furthermore, the 58 patients who received flumatinib as post-line therapy were divided into two groups based on the timing of switching to flumatinib: an early conversion group (n=18) and a late conversion group (n=40). The molecular responses and outcomes were assessed at multiple time points (3, 6, 9, and 12 months) during the treatment of flumatinib, along with the observation of adverse reactions.

Results: Flumatinib exhibited notable efficacy and safety as a therapeutic option for patients with chronic phase CML, whether utilized as a first-line or post-line treatment.