Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial

• Published in: Journal of hematology and oncology Vol. 17; no. 1; pp. 79 - 5
• Main Authors: Lu, Jing, Qiu, Huiying, Wang, Ying, Zhou, Xin, Dai, Haiping, Lu, Xuzhang, Yang, Xiaofei, Gu, Bin, Hong, Ming, Miao, Miao, Lu, Ruinan, Wang, Jun, Wu, Qian, Xue, Mengxing, Wang, Yun, Deng, Ailing, Shen, Yaoyao, Liu, Yin, Dou, Xueqing, Lei, Yutian, Wu, Depei, Zhu, Yu, Chen, Suning
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.09.2024; BioMed Central; BMC
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adolescent; Adult; Adults; Aged; Antibodies, Bispecific - administration & dosage; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell precursor acute lymphoblastic leukemia; Blinatumomab; Blood; Bone marrow; Cancer; CD19 antigen; Chemotherapy; Chromosomes; Correspondence; Cytokine storm; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Dexamethasone - therapeutic use; Female; Flow cytometry; Health risk assessment; Humans; Induction Chemotherapy - methods; Induction therapy; Induction treatment; Kinases; Leukemia; Leukocytes; Lymphatic leukemia; Lymphocytes B; Male; Medical prognosis; Middle Aged; Neurotoxicity; Philadelphia chromosome; Philadelphia chromosome-negative; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Product development; Reduced-dose chemotherapy; Remission; Remission (Medicine); Remission Induction; Sepsis; Thrombocytopenia; Young Adult; Pennsylvania; B-cell precursor acute lymphoblastic leukemia; Philadelphia chromosome-negative; Induction treatment; Blinatumomab; Reduced-dose chemotherapy
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-024-01597-8

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.