Efficacy and safety of olverembatinib in adult BCR::ABL1‐positive ALL with T315I mutation or relapsed/refractory disease

• Published in: British journal of haematology 2024-12, Vol.205 (6), p.2228-2233
• Main Authors: Liu, Weiyang, Wang, Cheng, Ouyang, Wanyan, Hao, Jie, Ren, Jiayi, Peng, Lijun, Tang, Sijie, Liu, Yuanfang, Zhu, Yongmei, Weng, Xiangqin, Jing, Duohui, Chen, Saijuan, Wang, Jin, Mi, Jian‐Qing
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Adolescent; Adult; Aged; Allografts; BCR::ABL1‐positive ALL; Chronic myeloid leukemia; Drug Resistance, Neoplasm; efficacy; Female; Fusion Proteins, bcr-abl - genetics; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Leukemia; Male; Middle Aged; Minimal residual disease; Mutation; Neoplasm, Residual; olverembatinib; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Recurrence; Remission; safety; Stem cell transplantation; T315I mutation; Treatment Outcome; Tyrosine kinase inhibitors; Young Adult
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.19804

Summary Third‐generation tyrosine kinase inhibitors (TKIs) have much potential for the treatment of BCR::ABL1‐positive leukaemia, particularly that harbouring the ABL1 T315I mutation. Olverembatinib (HQP1351), a novel third‐generation TKI, has favourable efficacy and safety profiles in chronic myeloid leukaemia. Here, we present the clinical findings from 31 BCR::ABL1‐positive acute lymphoblastic leukaemia (ALL) patients who received olverembatinib. Among the 14 patients with overt relapsed/refractory (R/R) disease (including 10 with the T315I mutation), 71.4% achieved an overall response. Of the other 17 patients with minimal residual disease (MRD)‐positive ALL (including 14 with the T315I mutation), 60.0% and 47.1% achieved MRD flow negativity and complete molecular remission, respectively. With a median follow‐up time of 16.3 months, the median event‐free survival and overall survival were 3.9 and 8.3 months respectively, in overt R/R patients, and 11.5 and 18.4 months in MRD‐positive patients. Allogeneic haematopoietic stem cell transplantation further improved outcomes among responders. The safety profile was generally manageable. This study suggests that olverembatinib‐based therapy is another promising option for BCR::ABL1‐positive ALL in addition to ponatinib, especially for patients with MRD‐positive disease and a single T315I mutation. Olverembatinib (HQP1351), a novel third‐generation tyrosine kinase inhibitor (TKI), has demonstrated impressive efficacy and safety in chronic myeloid leukaemia. This study aimed to investigate its potential application in adults with BCR::ABL1‐positive acute lymphoblastic leukaemia (ALL). Among the 14 patients with overt relapsed/refractory (R/R) disease, 71.4% achieved an overall response. Meanwhile, for 17 patients with minimal residual disease (MRD)‐positive ALL, 60.0% achieved MRD flow negativity, and 47.1% reached complete molecular remission (CMR). In addition, patients with MRD‐positive disease or harbouring a single T315I mutation both exhibited a significant survival advantage. Allo‐HSCT further improved clinical outcomes. This study indicates that olverembatinib could serve as a promising therapeutic option for BCR::ABL1‐positive ALL.