Hansoh Xinfu (flumatinib) / Jiangsu Hengrui Pharma, Jiangsu Hansoh Pharma - LARVOL DELTA

Efficacy and safety of pegylated interferon alfa-2b combined with tyrosine kinase inhibitors in chronic Phase chronic myeloid leukemia patients with TKI resistance or intolerance (ASH 2025) - "Median follow-up was 72 weeks (range 24-96).Prior TKIs included imatinib, nilotinib, dasatinib, flumatinib,and olverembatinib.By June 30,2025.Sixteen, fourteen, ten, and eight patients completed therapy at weeks 24,48,72,and 96,respectively.Nine patients discontinued treatment due to adverse events.Molecular responses:Week 24: MMR 37.5% (6/16),DMR 6.3%(1/16),Week 48:MMR57.1% (8/14); Week 72: MMR40.0% (4/10); DMR 30.0% (3/10); Week 96: MMR 50.0% (4/8),DMR 25.0% (2/8).Safety:The most common AEs were flu-like symptoms and hematologic toxicities (predominantly grade 1-2).Dose reductions or extended dosing intervals (up to q2 weeks) of PEG IFNα-2b were implemented to manage AEs. Conclusion PEG IFNα-2b combined with TKIs significantly reduces BCR::ABL1 transcript levels, enabling patients with TKI-resistant or intolerant chronic-phase chronic myeloid leukemia (CP-CML) to achieve major molecular response (MMR) and even deep molecular response (DMR), with a favorable safety..."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • IFNA1

Association of combined IKZF1plus genotype and ABL1 mutations with outcomes in adult BCR::ABL1-positive acute lymphoblastic leukemia (ASH 2025) - P=N/A | "The patients received a TKI-based [imatinib or flumatinib (a second-generation TKI)] standardized VIP regimen (Vincristine/Idarubicin/Prednisone), and eligible patients were recommended to undergo allo-HSCT. Notably, IKZF1 plus patients harboring T315I mutation constitute a subgroup with dismal survival, likely associated with the down-regulation of p53 pathways, and they would benefit from allo-HSCT. Conversely, IKZF1 plus cases without ABL1 mutations exhibit a markedly favorable prognosis."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • ABL1 • IKZF1

Clinical features and outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia: A 15-year retrospective study (ASH 2025) - "Among the frontline TKIs, the first-generation TKI imatinib has the highest usage rate(45.3%), followed by the second-generation TKIs dasatinib (32.3%) and flumatinib (8.7%). 4.8% of patientsreceived frontline olverembatinib treatment...Patients with ACAs have theworst prognosis compared to those with normal karyotype and Ph alone karyotype, and the impact isless significant under the allogeneic transplantation model. A complex karyotype is an independentunfavorable factor that significantly impacts the prognosis."

IO biomarker • Retrospective data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • ABL1 • BCR • RUNX1 • SETD2

Clinical and molecular features associated with glucolipid metabolic disorders and cardio-/cerebro-vascular adverse events in CML patients receiving olverembatinib therapy (ASH 2025) - "22 (13%) patients experienced imatinib failure only; 50 (30%), imatinib,dasatinib and/or flumatinib therapy failure; and 95 (57%) had a history of nilotinib exposure. Higher total cholesterol, more priorTKI-therapy lines, particularly prior nilotinib exposure, the presence of ASXL1, FAT4 and/or TET2mutations were the independent predictors for glucolipid metabolic disorders, CCVAEs andarterial/venous occlusive events. These clinical and molecular features may guide early risk identificationand targeted surveillance."

Adverse events • Clinical • Cerebral Hemorrhage • Chronic Myeloid Leukemia • Congestive Heart Failure • Diabetes • Dyslipidemia • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ABL1 • ASXL1 • FAT4 • TET2

Treatment-free remission outcomes in pediatric chronic myeloid leukemia: Second-generation TKIs vs. Imatinib–a real-world multicenter study from China (ASH 2025) - "Background Studies have demonstrated that a subset of adult chronic myeloid leukemia (CML) patients achievingdeep molecular response (DMR) for ≥2 years with tyrosine kinase inhibitor (TKI) therapy can successfullydiscontinue treatment and maintain treatment-free remission (TFR), thereby reducing long-term drugtoxicity and financial burden. However, data on TFR in pediatric CML remain limited, particularlyregarding whether second-generation TKIs (e.g.,nilotinib, dasatinib) confer superior TFR rates comparedto first-generation imatinib (IM) in real-world pediatric populations.MethodsThis retrospective multicenter study analyzed clinical data from 54 CML chronic-phase patients aged <18years who discontinued TKI therapy between September 2016 and September 2024 across nine Chinesehematology centers.Patients were stratified into IM and second-generation TKI groups based on pre-discontinuation therapy.Baseline characteristics were compared using Mann-Whitney U and χ²..."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Pediatrics

Updated efficacy and safety of olverembatinib (HQP1351) as second-line therapy in patients (pts) with chronic Phase-chronic myeloid leukemia (CP-CML) (ASH 2025) - P2 | "Twelve (25.5%) pts hadreceived imatinib as first-line, and 35 (74.5%) had been treated with a second-generation TKI, includingdasatinib (n = 7, 14.9%), nilotinib (n = 13, 27.7%), or flumatinib (n = 15, 31.9%), as first-line. Olverembatinib-related SAEs included platelet count decreased (6.4%) and anemia,myelosuppression, and pyrexia (2.1% each). No deaths were reported.ConclusionsOlverembatinib may provide a viable second-line treatment option for pts with CP-CML, especially thosewith disease failing first-line second-generation TKIs."

Clinical • Cardiovascular • Chronic Myeloid Leukemia • Hypertension • Neutropenia • Thrombocytopenia • ABL1 • BCR

Flumatinib versus nilotinib as first-line therapy for chronic myeloid leukemia in chronic Phase: A propensity score-matched cohort study (ASH 2025) - "Flumatinib is more likely to cause diarrheaand renal function impairment, while nilotinib is mainly characterized by elevated bilirubin and lipaselevels. ConclusionThe overall efficacy of flumatinib and nilotinib as first-line therapies for CML-CP is comparable, but thereare significant differences in their toxicity profiles."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

What is the optimal threshold for aberrant lymphoblasts at diagnosis to predict lymphoid transformation in chronic myeloid leukemia? (ASH 2025) - "Initial TKIs included imatinib (n = 776, 72%),nilotinib (n = 135, 12%), dasatinib (n = 42, 4%), and flumatinib (n = 127, 12%). Low-level ALB detected by FCM at diagnosis in chronic phase patients with CML predictedhigh possibility of subsequent lymphoid transformation during TKI therapy, especially in those with ALB≥0.4%."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

Olverembatinib-mediated deep remission improves allogeneic stem cell transplantation outcome in patients with blast crisis chronic myeloid leukemia: First real-world practice report (ASH 2025) - "All patients receivedTKIs+chemotherapy before transplantation and were stratified by pre-transplant TKIs exposure: 1/2G-TKIcohort (n=42, imatinib, nilotinib, flumatinib or dasatinib) versus olverembatinib (n=21, HQP1351), withbalanced baseline characteristics. This real-world analysis provides the first clinical evidence supporting the efficacy and safetyof olverembatinib in transplant-eligible BC-CML. Olverembatinib significantly enhances pre-transplantmolecular responses, compared to 1/2G-TKIs, associating with improved survival and reduced NRM inBC-CML patients receiving allo-HSCT. With a manageable safety profile, olverembatinib represents apromising bridging strategy prior to allo-HSCT, potentially redefining frontline management of BC-CML."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Thrombosis • Transplantation • ABL1 • ASXL1 • IKZF1 • RUNX1

Fixed-dose inotuzumab ozogamicin combined with vincristine and prednisone regimen as induction therapy for newly diagnosed B-cell acute lymphocytic leukemia (ASH 2025) - P=N/A | "All of them acceptedTKIs, four with imatinib, one with dasatinib and four with flumatinib. The fixed-dose INO combined with VP regimen can be regarded as a highly effective and low-toxicityinduction therapy for newly diagnosed patients for both Ph- B-ALL and Ph+ B-ALL."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Respiratory Diseases • ABL1 • BCR • IKZF1 • NRAS

Venetoclax Combined with Hypomethylation Agents As Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia - Priliminary Results from a Real World Study in China (ASH 2023) - "Five patients were treated with specific targeted drugs along with decitabine and azacitidine, one patient was treated with flumatinib, two patients were treated with gititinib, and one patient was treated with sorafenib. In this study, venetoclax in combination with a hypomethylation agent showed comparable responses across all genetic subgroups in this real-world study of China,which was compared to the results of clinical studies conducted primarily in Western countries. Currently, we have collected 800 samples in this study. We will analyze and report the short- and long-term efficacy of venetoclax plus hypomethylating agent for the treatment of newly diagnosed AML in the near future."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase II Study of Flumatinib with Chemotherapy for Newly Diagnosed BCR: : ABL1-Positive Acute Lymphoblastic Leukemia in Adults: Updated Results from RJ-ALL2020.2A Trial (ASH 2023) - P=N/A | "It has shown better efficacy compared to imatinib in clinical trials of CML, but few reports are available in ALL...Once the diagnosis is confirmed, the combination of flumatinib (600mg/day) and VIP-based chemotherapy regimen (Vincristine/Idarubicin/Prednisone) is given promptly...Blinatumomab is allowed to administer for MRD clearance before allo-HSCT...Achieving MRD flow negativity or CMR at 3 months and bridging allo-HSCT could further improve survival. The long-term follow-up data will be disclosed soon."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Central Nervous System Leukemia • Hematological Malignancies • Infectious Disease • Respiratory Diseases • ABL1 • BCR

Effect of Previous Differential Treatments on the Efficacy after Switching to Flumatinib in Patients with Chronic Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi) - "Compared with the previous treatment with other tyrosine kinase inhibitors (TKIs), initial use of flumatinib at diagnosis enable patients to achieve deeper molecular remission more rapidly. Compared with previous use of imatinib or nilotinib, previous use of dasatinib is associated with deeper molecular remission after switching to flumatinib."

Journal • Retrospective data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Chemotherapy-Free Treatment with Venetoclax, Azacitidine and Flumatinib Induces an Early and Deep Molecular Response in Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia:What Is the Underlying Mechanism? (ASH 2024) - "Azacitidine and flumatinib enhance venetoclax-induced apoptosis in Ph+ALL cells by upregulating pro-apoptotic proteins NOXA and BIM, and downregulating the anti-apoptotic protein MCL-1. Our study provided a theoretical foundation for the clinical efficacy of VAF regimen."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ANXA5 • BBC3 • BCL2L1 • BCL2L11 • BCR • CASP3 • MCL1 • PMAIP1

Flumatinib for the Treatment of Adult Patients with Resistant or Intolerant Chronic-Phase Chronic Myeloid Leukemia: Results from Real-World Data (ASH 2023) - "Prior therapies included imatinib, dasatinib, nilotinib, olverembatinib, radotinib and ponatinib. 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."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Real-World Safety and Clinical Response of Flumatinib in the Treatment of Chronic Myeloid Leukemia: A Retrospective Study (ASH 2023) - "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. In comparison to imatinib, initial administration of flumatinib resulted in more profound and expeditious molecular responses. The utilization of flumatinib as a post-line therapeutic approach during the early stage of treatment exhibits a favorable influence on patient prognosis."

Real-world • Real-world evidence • Retrospective data • Chronic Myeloid Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia

Safety and Efficacy of Flumatinib in Patients with Chronic Myeloid Leukemia Resistant or Intolerant to Imatinib (ASH 2023) - "This retrospective study had suggested promising effects of flumatinib, which showed induced high rates of CCyR and MMR or DMR in patients resistant or intolerant to imatinib. The incidence of AEs during flumatinib treatment was tolerable."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • ABL1

Flumatinib Versus Imatinib As a Frontline Therapy for Patients with Chronic Myeloid Leukemia in Chronic Phase: A Propensity Score Matching Study from Real-World Data (ASH 2023) - "Mechanistically, with its structure of trifluoromethyl and pyridine flumatinib blocked BCR-ABL1 kinase autophosphorylation with much more potent activity than did imatinib and even showed higher efficacy than nilotinib against wild-type BCR-ABL1 kinase. The real-world data demonstrated that as a first-line treatment setting, flumatinib can bring patients with chronic phase CML higher rates of responses, and faster and deeper responses, indicating that flumatinib could be an alternative effective first-line treatment for CML-CP. The adverse events of flumatinib, such as cardiovascular events, abnormal liver function, and diarrhea, need to be given continuous concern in future studies."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Olverembatinib (HQP1351) Combined with Chemotherapy Is an Effective and Safe Treatment in Patients with Philadelphia Chromosome-Positive (Ph +) Acute Lymphoblastic Leukemia (ALL) and Chronic Myeloid Leukemia in Lymphoid Blast Phase (CML-LBP) That Failed TKI-Based Regimens (ASH 2023) - "The 15 R/R patients (11, Ph + ALL; 4, CML-BP) received olverembatinib 30 or 40 mg on alternate days combined with VP (vindesine 4 mg once per week for 4 weeks and prednisone 1 mg/kg for 3 weeks and tapered at the fourth)...Among the 16 patients with molecular resistance to TKI-based chemotherapy (imatinib [n = 4]; dasatinib [n = 9]; flumatinib [n = 3]), 2 received olverembatinib monotherapy, 7 olverembatinib plus VP, and 7 hyper-CVAD, of whom 8 received subsequent allogeneic transplantation...Treatment-related nonhematologic severe adverse events were observed in 3 patients, including (each) stable angina pectoris, severe pneumonia, and fatal Klebsiella sepsis. Conclusions Olverembatinib-based chemotherapy is effective and safe in patients with R/R and molecular resistant Ph + ALL or CML-LBP."

Clinical • Acute Lymphocytic Leukemia • Central Nervous System Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock • ABL1

Suppressing IKZF1 Deletion-Mediated Activation of Ras Oncogenic Signaling By the Combination of Azacitidine and Flumatinib in High-Risk B-ALL (ASH 2023) - "Moreover, about 80% of Ph +B-ALL patients have the IKZF1 deletion, our ChIP-seq data showed that IKZF1-encoded Ikaros protein binds to the promoter region of PTPN11 and CK2 inhibitor CX4945 as Ikaros function activator dramatically increase the Ikaros binding to the promoter of PTPN11 in B-ALL cells and Ikaros directly suppresses its promoter activity (Fig. Conclusions The combination of AZA and FLU has a synergistic anti-leukemia effect on cell proliferation arrest and apoptosis in Ph +ALL cells with IKZF1-deletion by targeting Ikaros/PTPN11/Ras oncogenic signaling. Our data provide experimental evidence for a new potential combination of AZA with FLU in the therapy of Ph +ALL and highlight the likelihood of the novel combination in ALL patients."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BCL2 • CDKN1A • IKZF1 • PTPN11

Flumatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: An Open-Label, Multi-Center Study (ASH 2023) - P=N/A | "And some current clinical trials revealed that flumatinib has been shown to be a more potent inhibitor of BCR::ABL than imatinib. None of the patients discontinued or died due to AEs. Conclusion Flumatinib as first-line therapy in patients with newly diagnosed CP-CML was not inferior to nilotinib and dasatinib and well tolerated."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

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 (ASH 2023) - "In addition, if the patients were switched to flumatinib earlier, the optimal response was achieved faster. The grade 3/4 AEs were mainly hematologically related, whereas the gastrointestinal events were mostly of grade 1-2."

Clinical • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Oncology • Thrombocytopenia • ABL1 • BCR

A Predictive Scoring System for Therapy Failure of Tyrosine-Kinase Inhibitors in Patients with Chronic-Phase Chronic Myeloid Leukemia (ASH 2023) - "Results In the training dataset, 1,591 patients (78%) initially received imatinib; 326 (16%), nilotinib; 85 (4%), dasatinib; and 36 (2%), flumatinib (a novel 2G-TKI made in China). Moreover, patients identified as intermediate- or high-risk cohorts by the predictive scoring system receiving initial 2G-TKI-therapy had significantly-lower therapy failure rate than those receiving imatinib-therapy (p-values = 0.002 and 0.017) both in the training and validation datasets. Conclusions We developed and validated a robust predictive scoring system for TKI-therapy failure in newly-defined CML-CP patients according to the WHO criteria (5th edition, 2022), which might help physicians decide appropriate therapy strategy."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Flumatinib Versus Nilotinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia (ASH 2023) - P=N/A | "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. Conclusion The efficacy of flumatinib is comparable to nilotinib in Chinese patients with newly diagnosed Ph+ CML-CP. The overall incidences of grade 3-4 AEs were also accessible for the two drugs, nevertheless, a few AEs inclusively hepatic toxicity, anemia and skin toxicity were remarkably lower with flumatinib intervention."

Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Oncology • BCR

Flumatinib with Low-Intensity Chemotherapy in Elderly Patients with Newly Diagnosed BCR::ABL1-Positive Acute Lymphoblastic Leukemia (ASH 2024) - "All pts received flumatinib (600mg/day) and VP-based (Vincristine/Prednisone) chemotherapy; dose reduction was permitted according to the discretion of physicians. Central nervous system (CNS) prophylaxis is regularly performed by intrathecal injection of methotrexate, cytarabine, and dexamethasone after the induction course...The clinical outcomes observed for flumatnib were comparable to those reported for the classical second-generation TKI dasatinib. These findings will be further validated through long-term follow-up with an expanded sample size."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Central Nervous System Leukemia • Chronic Myeloid Leukemia • Infectious Disease • Pancreatitis • Respiratory Diseases • ABL1 • CDKN2A • CDKN2B • IKZF1 • PAX5