A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor (TKI) Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) in Adults

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

Start Date25 Jan 2021

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

100 Translational Medicine associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

0 Patents (Medical) associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

391

Literatures (Medical) associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

01 Dec 2024·British Journal of Haematology

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

Article

Author: Liu, Yuanfang ; Tang, Sijie ; Chen, Saijuan ; Ren, Jiayi ; Wang, Cheng ; Ouyang, Wanyan ; Peng, Lijun ; Weng, Xiangqin ; Hao, Jie ; Wang, Jin ; Liu, Weiyang ; Mi, Jian‐Qing ; Jing, Duohui ; Zhu, Yongmei

SummaryThird‐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.

01 Sep 2024·Cancer Diagnosis & Prognosis

Association of PARP1 Expression Levels and Clinical Parameters in Different Leukemic Subtypes With BCR::ABL1 p190+ Translocation

Article

Author: DE Pinho Pessoa, Flávia Melo Cunha ; Ribeiro, Rodrigo Monteiro ; DA Silva, Jean Breno Silveira ; SEABRA, ALINE DAMASCENO ; DE Sousa Oliveira, Deivide ; Dias Nogueira, Beatriz Maria ; DE Moraes Filho, Manoel Odorico ; Burbano, Rommel Rodriguez ; DE MORAIS, GUILHERME PASSOS ; MELLO JÚNIOR, FERNANDO AUGUSTO RODRIGUES ; Moreira-Nunes, Caroline Aquino ; Seabra, Aline Damasceno ; BURBANO, ROMMEL RODRIGUEZ ; DE MORAES FILHO, MANOEL ODORICO ; DE PINHO PESSOA, FLÁVIA MELO CUNHA ; DE Moraes, Maria Elisabete Amaral ; Mello Júnior, Fernando Augusto Rodrigues ; Machado, Caio Bezerra ; Khayat, André Salim ; MOREIRA-NUNES, CAROLINE AQUINO ; DA SILVA, JEAN BRENO SILVEIRA ; DIAS NOGUEIRA, BEATRIZ MARIA ; MACHADO, CAIO BEZERRA ; RIBEIRO, RODRIGO MONTEIRO ; DE Morais, Guilherme Passos ; DE SOUSA OLIVEIRA, DEIVIDE ; KHAYAT, ANDRÉ SALIM ; DE MORAES, MARIA ELISABETE AMARAL

Background/Aim: Although the reciprocal translocation t(9;22)(q34;q11) is a hallmark of chronic myeloid leukemia (CML), it is also present in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Depending on the gene's breakpoint, it is possible to obtain three isoforms, among which p190 stands out for the poor prognosis it induces whenever it appears. Due to the genomic instability induced by BCR::ABL1, it is proposed to expand the applicability of poly-ADP-ribose polymerase-1 (PARP1) and its inhibitors in hematological neoplasms. Materials and Methods: We measured the expression levels of PARP1 by quantitative real-time PCR (qPCR) using TaqMan®, correlating its expression with BCR::ABL1 p190+, to evaluate its influence in the clinic of adult patients. Results: We found that PARP1 is expressed differently in ALL, AML and CML and that p190 transcripts do not follow a linear pattern in these populations. We also found that PARP1 expression is not correlated with age, white blood cell and the amount of p190 transcripts. Conclusion: Despite the lack of statistical correlation between the variables analyzed, the role of PARP1 in BCR::ABL1 leukemia cannot be ruled out, given the instability profile promoted by this translocation. Finally, further studies involving a larger sample of patients are needed, as well as investigations into other molecular pathways that may impact on the pathogenesis of different BCR::ABL1 leukemic subtypes.

14 Jul 2024·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

[The progress in classification and prognosis evaluation of BCR::ABL1 positive acute lymphoblastic leukemia].

Review

Author: Wang, J ; Wang, C ; Mi, J Q ; Yan, Y C

The application of tyrosine kinase inhibitors and targeted immunotherapy has revolutionized the therapeutic strategies and clinical outcome for BCR::ABL1-positive B-cell acute lymphoblastic leukemia (BCR::ABL1(+) B-ALL). The classification was updated successively by the World Health Organization and the International Consensus Classification in 2022. The risk stratification of this entity, for the first time, was modified by the National Comprehensive Cancer Network in 2023, both minimal residual disease assessment and IKZF1(plus) genotyping recognized as critical prognostic factors. These important updates would have significant implications for clinical management. Therefore, this review focused on the latest advances in the classification and prognostic evaluation of BCR::ABL1(+) B-ALL.

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