Therapeutic Options for Patients with TP53 Deficient Chronic Lymphocytic Leukemia: Narrative Review

Stefaniuk, Paulina; Onyszczuk, Julia; Szymczyk, Agnieszka; Podhorecka, Monika

doi:10.2147/cmar.s283903

Cited by 8 publications

(2 citation statements)

References 110 publications

(176 reference statements)

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“…p53 activation leads to the elimination or repair of damaged cells, in order to reduce the risk of propagating mutations [ 68 ]. In approximately 60% of malignant neoplasms in humans, TP53 is mutated or inactivated [ 58 , 69 ]. The presence of TP53 mutation is also shown to be one of the most important factors of poor prognosis in t-AML.…”

Section: Therapy-related Amlmentioning

confidence: 99%

In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

Stefaniuk

Szymczyk

Podhorecka

2022

JCM

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Secondary acute myeloid leukemia can be divided into two categories: AML evolving from the antecedent hematological condition (AHD-AML) and therapy related AML (t-AML). AHD-AML can evolve from hematological conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, MDS/MPN overlap syndromes, Fanconi anemia, and aplastic anemia. Leukemic transformation occurs as a consequence of the clonal evolution—a process of the acquisition of mutations in clones, while previous mutations are also passed on, leading to somatic mutations accumulation. Compared de novo AML, secondary AML is generally associated with poorer response to chemotherapy and poorer prognosis. The therapeutic options for patients with s-AML have been confirmed to be limited, as s-AML has often been analyzed either both with de novo AML or completely excluded from clinical trials. The treatment of s-AML was not in any way different than de novo AML, until, that is, the introduction of CPX-351—liposomal daunorubicin and cytarabine. CPX-351 significantly improved the overall survival and progression free survival in elderly patients with s-AML. The only definitive treatment in s-AML at this time is allogeneic hematopoietic cell transplantation. A better understanding of the genetics and epigenetics of s-AML would allow us to determine precise biologic drivers leading to leukogenesis and thus help to apply a targeted treatment, improving prognosis.

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Section: Therapy-related Amlmentioning

confidence: 99%

In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

Stefaniuk

Szymczyk

Podhorecka

2022

JCM

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“…The most clinically significant markers of poor disease outcome are the lack of mutations in the immunoglobulin heavy chain variable region locus ( IGHV ), deletion of chromosome 11q or 17p, as well as high expression of ZAP-70 (zeta-associated protein 70) and CD38 [ 1 , 2 , 3 ]. Moreover, recurrent genetic abnormalities, such as TP53 , ATM , NOTCH1 , SF3B1 , BIRC3 , and MYD88 mutations are associated with disease prognosis, and some of them may influence treatment decisions [ 3 , 5 , 6 ]. Among different biomarkers, microRNAs (miRNAs) have appeared as new diagnostic and therapeutic biomarkers in CLL patients [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia

Chocholska

Zarobkiewicz

Szymańska

et al. 2023

IJMS

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The aim of this study was to investigate the expression of miR-17∼92 cluster members in chronic lymphocytic leukemia (CLL) patients. Six microRNAs (miRNAs)—miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1—very poorly characterized in CLL patients, were chosen for the study to consider their possible role as cancer biomarkers. It is currently unclear to which extent miR-17~92 expression is related to other routinely measured CLL markers, and whether the findings can be of any clinical significance. To achieve this goal, we report the expression levels of these miRNAs detected by RT-qPCR in purified CD19+ B lymphocytes of 107 CLL patients and correlate them with existing clinical data. The study provides new evidence regarding the heterogeneity of miR-17~92 cluster members’ expression in CLL patients. Higher miR-17-5p expression was associated with unfavorable prognostic factors (i.e., 17p and 11q deletions, CD38 and ZAP-70 expression). On the other hand, miR-19a, miR-20a, and miR-92a-1 negatively correlated with these adverse factors. The presence of del(13q) as a sole aberration was associated with a significantly lower miR-17-5p as well as higher miR-19a-3p and miR-92a-1-5p expression compared to patients carrying unfavorable genetic aberrations. Particularly, miR-20a could be considered an independent favorable prognostic factor. In a multivariate analysis, high miR-20a expression remained an independent marker predicting long TTT (time to treatment) for CLL patients.

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Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE

Zhou,

Wang,

Pan

et al. 2024

Ann Hematol

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs. ibrutinib to treat relapsed/refractory (R/R) CLL/SLL. Here we report results from the subgroup of Chinese patients. Adults with R/R CLL/SLL were randomized 1:1 to receive zanubrutinib (160 mg twice-daily) or ibrutinib (420 mg once-daily) until disease progression or unacceptable toxicity. Endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Data were analyzed descriptively. Ninety patients were randomized in China (zanubrutinib, n = 47; ibrutinib, n = 43). Baseline characteristics were balanced between groups, with fewer male patients in the zanubrutinib vs. ibrutinib group (55.3% vs. 69.8%). Median age was 60.5 years, 11% had del(17p) mutation, and 32% had tumor protein 53 (TP53) mutation. With median 25.3 months follow-up, ORR was 80.9% with zanubrutinib vs. 72.1% with ibrutinib. PFS was improved with zanubrutinib vs. ibrutinib (HR = 0.34 [95% CI, 0.15, 0.77]), and the HR for OS was 0.45 (95% CI, 0.14, 1.50). Rates of Grade ≥ 3 treatment-emergent adverse events (TEAEs; 64.4% vs. 72.1%), AEs leading to discontinuation (6.4% vs. 14.0%), and serious TEAEs (35.6% vs. 51.2%) were lower with zanubrutinib vs. ibrutinib. Zanubrutinib demonstrated improved ORR, PFS, and OS vs. ibrutinib and a more favorable safety profile in patients with R/R CLL/SLL in China. These results are consistent with the full global population of ALPINE. ClinicalTrials.gov: NCT03734016, registered November 7, 2018.

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Therapeutic Options for Patients with TP53 Deficient Chronic Lymphocytic Leukemia: Narrative Review

Cited by 8 publications

References 110 publications

In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE

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