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

Real-World Efficacy and Safety of Flumatinib as the first-line treatment in Patients with de novo Philadelphia-positive Acute Lymphoblastic Leukemia (Clin Lymphoma Myeloma Leuk) - "At 24 months, OS and EFS were 87.4% and 62.6%, respectively. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved EFS (p<0.0001) and tended to improve OS (p=0.0503). Common hematologic AEs included neutropenia (93.8%) and thrombocytopenia (76.9%); severe non-hematologic AEs were rare. Relapses (17/63) predominantly associated with T315I (10/19) and Y253H (5/19) mutations. Age≥35 years, BCR/ABL1P210 and ABL1 Y253H mutation were significantly associated with worse OS."

Retrospective data • Acute Lymphocytic Leukemia

Blinatumomab in combination with olverembatinib and concurrent intrathecal chemotherapy successfully treated a chronic myeloid leukemia relapse with central nervous system blast crisis: case report and literature review. (PubMed, Ann Hematol) - "The combination of blinatumomab, olverembatinib, and concurrent intrathecal chemotherapy may be an effective treatment strategy for CML progression, particularly in cases with CNS involvement."

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

Treatment of JAK2 V617F-positive primary myelofibrosis and advanced chronic myelogenous leukemia with ruxolitinib and flumatinib: a case report. (PubMed, Ann Med Surg (Lond)) - "In the current case, the BCR-ABL fusion was detected and CML was confirmed after the recurrence of splenomegaly. Subsequent treatment with a combination of flumatinib and ruxolitinib was demonstrated to be safe and effective."

Journal • Chronic Myeloid Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis • ABL1 • BCR • CALR • JAK2

Molecular response of a patient with e19a2-positive chronic myeloid leukemia to flumatinib: a case report and literature review. (PubMed, Front Med (Lausanne)) - "Patients with the e19a2 transcript often show poor response to first-line treatment with imatinib, and no standard therapy has been established for this subtype...Following treatment discontinuation and prednisone therapy, the patient continued dasatinib (80 mg/d)...The patient was then switched to flumatinib (600 mg/d), achieving major molecular response (MMR) at 6 months and deep complete molecular response (MR4.5) at 24 months, with good tolerance. Flumatinib demonstrated excellent deep molecular response and good tolerability in e19a2-positive CML patients, suggesting that it may be one of the preferred treatment options for such patients."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Respiratory Diseases • ABL1

Isolated Central Nervous System Infiltrated and Progressed to Acute Myeloid Leukemia from Chronic Myeloid Leukemia with e1a3 BCR-ABL1 Transcript: A Rare Case Report and Literature Review. (PubMed, Cancer Manag Res) - "Following initial diagnosis, the patient was treated with the tyrosine kinase inhibitor (TKI) Flumatinib. The patient remains disease-free following olverembatinib maintenance therapy. This case underscores the importance of comprehensive diagnostic apporsches and the potential efficacy of third-generation TKIs and allo-HSCT in the treatment of e1a3-type CML."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pain • Transplantation • ABL1 • BCR

Tyrosine Kinase Inhibitor Treatment Patterns in Patients With Chronic-Phase Chronic Myeloid Leukemia: A Single Center Data From China. (PubMed, Clin Lymphoma Myeloma Leuk) - "These findings emphasized the complexities involved in the management of patients with CP-CML and highlighted the importance of personalized treatment strategies."

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

Chronic myelogenous leukemia coexpressing V-e16a2, V-e13a2, e13a2, and e14a2 BCR::ABL1 fusion transcripts: a case report and review of the literature. (PubMed, Front Oncol) - "A 66-year-old Chinese female patient was diagnosed with chronic myeloid leukemia-chronic phase (CML-CP) expressing four BCR::ABL1 transcripts, including variant e16a2(V-e16a2), variant e13a2(V-e13a2), classical e13a2, and e14a2 transcripts. The patient was treated with flumatinib, a tyrosine kinase inhibitor (TKI).The variant transcripts reported exhibited a favorable response to TKI, and attention should be directed toward monitoring variant transcripts."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Differential in Vitro Sensitivity of BCR::ABL1 Kinase Domain Mutations to Tyrosine Kinase Inhibitors Depending on the p190 or p210 Background (ASH 2024) - "The resulting wildtype and 134 mutant Ba/F3 cell lines generated in this way, i.e. 67 cell lines carrying a large spectrum of single and compound mutations in the p190 and p210 background, respectively, were tested in vitro against different concentrations of eight TKIs including imatinib, nilotinib, dasatinib, bosutinib, ponatinib, vamotinib, asciminib, and flumatinib using the CellTiter-Glo® luminescent cell viability assay (Promega). The findings of the present study provided the basis for extending and supplementing the existing heatmaps for various mutations and TKIs in the background of p210 by a corresponding heatmap established specifically for mutations occurring in the background of p190, thus filling a clinically important information gap. Once appropriately evaluated in the clinical setting, the comprehensive heatmaps emanating from the present study may provide support for adequate TKI selection (and potentially for selection of the appropriate dose) in..."

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Olverembatinib As Second-Line (2L) Therapy in Patients (pts) with Chronic Phase-Chronic Myeloid Leukemia (CP-CML) (ASH 2024) - P2 | "Twelve (28.6%) pts had received 1L imatinib, and 30 (71.4%) had been treated with a 1L 2G TKI, including dasatinib (n = 5, 11.9%), nilotinib (n = 11, 26.2%), or flumatinib (n = 14, 33.3%). Conclusions This is the first study report of olverembatinib in 2L CP-CML treatment. Olverembatinib may provide an effective and safe 2L treatment option for pts with CP-CML, especially those failing on 1L 2G TKIs."

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

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

Tyrosine kinase inhibitor treatment patterns in patients with chronic-phase chronic myeloid leukemia: a single center data from China (Clin Lymphoma Myeloma Leuk) - "1766 patients receiving initial imatinib (n = 1374), nilotinib (n = 254), dasatinib (n = 63) and flumatinib (n = 75) therapy were retrospectively interrogated....TKI switches were mainly due to resistance (64%, 76%, 88% across lines) and intolerance (19%, 14%, 7%). Multivariable analyses revealed ELTS intermediate/high-risk group (vs. low-risk), male, and lower hemoglobin were significantly associated with a higher probability of TKI switch. Compared to imatinib, initial nilotinib or dasatinib had lower switch rates. Male and ELTS high-risk (vs. low/intermediate) were associated with resistance-related switches, while lower hemoglobin, older age and initial dasatinib or flumatinib (vs. imatinib) were associated with intolerance-related switches to second-line therapy. Second-line imatinib/flumatinib (vs. nilotinib/dasatinib) and no/non-specific ABL mutation were associated with resistance-related switches to third-line therapy."

Retrospective data • Chronic Myeloid Leukemia

Similar Efficacy and Distinct Safety Profile of Nilotinib, Dasatinib and Flumatinib in Chronic Myeloid Leukemia Patients Resistant or Intolerant to 1st Line Imatinib (ASH 2024) - "Side effects of concern were rash, bilirubin increasing, cholesterol elevation, thrombotic event and thyroid disease in nilotinib group; pleural effusion, increased pulmonary artery pressure, pericardial effusion, thrombocytopenia, and edema in dasatinib group; increased creatinine and thyroid disease in flumatinib group. Conclusion : The patients intolerant/resistant to imatinib receiving nilotinib, dasatinib or flumatinib as 2L therapy had similar molecular response and survival and suffered different side effects."

Clinical • Cardiovascular • Chronic Myeloid Leukemia • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Respiratory Diseases • Thrombocytopenia

High-Risk "Failure" Events Predicting Worse Survival in Patients with Chronic Myeloid Leukemia during Tyrosine Kinase Inhibitor Therapy (ASH 2024) - "1,632 (78%) patients received initial imatinib therapy; 460 (22%), 2G-TKI therapy (nilotinib, n = 313; dasatinib, n = 78; flumatinib, n = 69). In patients with the high-risk "failure" events, certain clinical co-variates such as the 2G- or 3G-TKI used, the lower HB, PLT and blood basophils, and the higher blasts can further predict the worse survival. These insights emphasize the need for vigilant monitoring the patients with high-risk "failure" events to implement tailored treatment strategies."

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

Low-Risk Group Identified By a Refined Prognostic System Integrating Both IKZF1plusgenotyping and MRD Assessment in Adult BCR::ABL1-Positive Acute Lymphoblastic Leukemia (ASH 2024) - P=N/A | "The patients were treated with a TKI-based [imatinib or flumatinib (a second-generation TKI)] standardized VDP regimen(vincristine/daunorubicin/prednisone), and eligible patients were recommended to undergo allo-HSCT (Clinical Trial Registration Number : ChiCTRONRC-14004968, ChiCTR2100042248 and ChiCRT2100044308). The low-risk group (non-IKZF1plus/MRD-), for the first time, was identified in adult BCR : : ABL1+ ALL. In the era of TKI combined with chemotherapy, it also suggested that allo-HSCT should be spared for the low-risk group, but is recommended for intermediate-risk and high-risk groups if eligible."

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

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 • Cardiovascular • Chronic Myeloid Leukemia • Infectious Disease • Pancreatitis • Respiratory Diseases • ABL1 • CDKN2A • CDKN2B • IKZF1 • PAX5

…Innovative Drugs of Hansoh Pharmaceutical Group have been Renewed in the National Reimbursement Drug List (2024 Version) (Hansoh Pharma Press Release) - "On November 28, 2024, Hansoh Pharmaceutical Group Company Limited announced that the following...innovative drugs of the Group had been renewed inthe National Reimbursement Drug List (2024 Version)....The 2024 NRDL will be officially implemented on January 1, 2025. (i) Aumolertinib Mesilate Tablets (trade name: Ameile) is the first domestic innovative...TKI drug independently developed by Hansoh, and its two approved indications have been renewed in the 2024 NRDL: The first-line treatment for adult patients with locally advanced or metastatic...NSCLC whose tumors have EGFR exon 19 deletions or exon 21(L858R) substitute mutation. The treatment of locally advanced or metastatic NSCLC in adult patients who have progressed on or after EGFR-TKI therapy, and have been confirmed to have EGFR T790M mutation positivity through testing; (ii) Flumatinib Mesylate Tablets (trade name: Hansoh Xinfu) is...used to treat adult patients with...Ph+CML in the chronic phase."

Reimbursement • Chronic Myeloid Leukemia • Non Small Cell Lung Cancer

Flumatinib Maintenance after Hematopoietic Stem Cell Transplantation for Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (APBMT 2024) - No abstract available

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Gynecomastia in a Chronic Myeloid Leukemia Patient After Switching from Imatinib to Flumatinib. (PubMed, Patient Prefer Adherence) - "This adverse event has also been associated with TKIs such as imatinib, dasatinib, and rarely nilotinib. Inspired by this case and through a review of the literature, we propose possible mechanisms and management strategies for this rare adverse event associated with TKIs, along with future perspectives. This may assist others in dealing with this issue and stimulate research on it."

Journal • Chronic Myeloid Leukemia • Endocrine Disorders • Hematological Malignancies • Leukemia • Oncology

Flumatinib combined with chemotherapy for newly diagnosed adult with Ph-positive acute lymphoblastic leukemia：a single-center, retrospective observational study (CSCO 2024) - No abstract available

Observational data • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Chronic myeloid leukemia during osimertinib treatment in a non-small cell lung cancer patient: A case report. (PubMed, Heliyon) - "While there is a potential association between EGFR-TKIs and the development of hematologic abnormalities such as CML, more evidence is needed to clarify whether EGFR-TKIs have a leukemogenic effect. For patients with CML during EGFR-TKIs treatment, osimertinib combined with flumatinib may be an effective treatment modalities and the side effects can be tolerated."

Journal • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Flumatinib combined with chemotherapy for newly diagnosed adult with Ph-positive acute lymphoblastic leukemia: A single-center, retrospective observational study (ESMO 2024) - "Flumatinib combined with multiagent chemotherapy as induction had a high level of efficacy in adult with newly diagnosed Ph+ ALL patient."

Observational data • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Comparative efficacy and safety of first-line tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and network meta-analysis. (PubMed, Transl Cancer Res) - "In terms of efficacy, second-generation TKIs such as dasatinib, nilotinib, and radotinib showed certain advantages in improving patients' MMR and CCyR compared to imatinib...Dasatinib more likely caused anemia, bosutinib thrombocytopenia, and imatinib neutropenia, whereas nilotinib and flumatinib might have better safety profiles in terms of severe hematologic adverse events...Thus, as each second-generation TKI has a distinct clinical efficacy and safety, and is associated with different economic factors, its choice should be dictated by the specific patient clinical conditions (patient's specific disease characteristics, comorbid conditions, potential drug interactions, as well as their adherence). Nevertheless, due to the limited number of original research, additional high-quality studies are needed to achieve any firm conclusion on which second-generation TKI is the best choice for that peculiar patient."

Journal • Retrospective data • Review • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Advances in basic and clinical research of flumatinib (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "Imatinib is the first generation of small molecule tyrosine kinase inhibitors (TKI) that revolutionized the treatment of CML. Flumatinib also showed a higher potency against CML with specific mutations, Ph(+) acute lymphoblastic leukemia and some solid tumors. The adverse events are manageable and tolerable."

Journal • Review • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML) (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Combination therapy • New P1 trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Overcoming flumatinib resistance in chronic myeloid leukaemia: Insights into cellular mechanisms and ivermectin's therapeutic potential. (PubMed, J Cell Mol Med) - "This cell line exhibited cross-resistance to imatinib and doxorubicin, but remained sensitive to the antiparasitic agent ivermectin, which possesses antitumoural effects. Collectively, the increased autophagy, higher expression of drug-efflux proteins and hyperactivation of the EGFR/ERK/STAT3 signalling pathway were identified as pivotal elements promoting resistance to flumatinib. The significant effects of ivermectin might offer a novel therapeutic strategy to overcome flumatinib resistance and optimize the treatment outcomes of CML."

Journal • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABCC1 • ABL1 • BCR