Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies

King, Amber C.; Peterson, Tim J; Horvat, Troy Z.; Rodríguez, Mabel; Tang, Longwen

doi:10.1177/1060028016685803

Cited by 31 publications

(24 citation statements)

References 33 publications

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“… 57 Obatoclax and venetoclax (ABT199) are BCL2 inhibitors which can be used for the treatment of relapsed/refractory HL and previously untreated FL while in combination with rituximab through restoring normal apoptosis. 58 , 59 , 60 …”

Section: Apoptosis Signaling Pathwaymentioning

confidence: 99%

Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies

Sun

Young

2018

Chronic Diseases and Translational Medicine

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Accumulating evidence confirmed that many dysregulated signaling pathways and aberrant genetic alterations contribute to the oncogenesis and heterogeneity of lymphoid malignancies. Therapeutically targeting dysregulating signaling pathways and their hidden oncogenic biomarkers are becoming available, but did not show desired therapeutic effect in current clinical practice. It is meaningful to further understand the underlying mechanisms of the dysregulated signaling pathways and to address the potential utility of pathway-related biomarkers. To precisely identify the dysregulation of signaling pathways and the “driver” oncogenic biomarkers, as well as to develop reliable and reproducible risk-stratification based on biomarkers will be challenging. Nevertheless, pathway-based targeted therapy will raise the hope to improve the outcomes of the patients with lymphoid malignancies, especially with aggressive types, and the efficient utility of pathway-related biomarkers in diagnosis, prognosis, prediction of lymphoid malignancies may also be able to power precision medicine.

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Section: Apoptosis Signaling Pathwaymentioning

confidence: 99%

Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies

Sun

Young

2018

Chronic Diseases and Translational Medicine

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“…In addition, with the development of targeted, less‐toxic therapies for lymphoma such as ibrutinib , acalabrutinib , and venetoclax , among others currently on clinical trials , “unfit” and “frail” elderly MCL patients stand to benefit more from their use in the frontline setting.…”

Section: Older MCL Patients With Risk Variablesmentioning

confidence: 99%

“…Also, frail old patients with MCL can be treated with the R-CVP regimen, in which anthracycline-like drugs are removed from the R-CHOP regimen due to cardiac toxicity. In addition, with the development of targeted, less-toxic therapies for lymphoma such as ibrutinib [83], acalabrutinib [84,85], and venetoclax [86], among others currently on clinical trials [87][88][89][90][91][92], "unfit" and "frail" elderly MCL patients stand to benefit more from their use in the frontline setting.…”

Section: R-chop-like Therapymentioning

confidence: 99%

Frontline Treatment for Older Patients with Mantle Cell Lymphoma

Desai

Zeng

et al. 2018

The Oncologist

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The natural history of mantle cell lymphoma (MCL) undergoing chemotherapy is a cyclical pattern of remission followed by recurrence of disease due to acquired chemotherapy resistance. The median age of the occurrence of MCL is 65 years, so half of the newly diagnosed MCL patients are considered "elderly." The tolerance to long-term chemotherapy in elderly patients is decreased; hence, the response to frontline therapy used is of paramount importance. We hope that our review may guide clinicians in treating such populations in a more personalized and evidence-based manner.In the older patients with risk variables, frontline treatment is determined according to different body status of fit, unfit or compromised, and frail. In the fit patients, the pursuit of remission and prolongation of survival might currently justify the use of more intense and toxic therapies. For unfit or compromised older patients, disease control needs to be prioritized, maintaining a balance between the benefits and toxicities of the treatment. For frail patients, tolerance of treatment and minimizing myelotoxicity should be the primary focus. "Chemotherapy-free" regimens are likely to be considered as the first-line strategy for this population. On the other hand, in the older MCL population without risk variables, observation or "watch and wait" can prevent overtreatment. Furthermore, more clinical trials and research studies on novel agents and targeted therapies need to be translated into the general population to provide optimal treatment and to guide personalized treatment. IMPLICATIONS FOR PRACTICE: This review emphasizes the importance of frontline therapies for older MCL patients. MCL patients commonly experience a cyclical pattern of remission followed by recurrence of disease due to acquired chemotherapy resistance. As a special population, elderly patients have various comorbidities and decreased organ function, which may reduce the chances of undergoing treatment for recurrent disease. Thus, this older population of patients with MCL should be treated separately and exceptionally. So far, systematic reviews with regard to frontline treatment for older patients with MCL have not been encountered, but the hope is that this review may guide clinicians in treating such populations in a more personalized and evidence-based manner.

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“…69,70 Venetoclax (ABT199), another BCL2 inhibitor, offers promise to patients with relapsed/refractory lymphoid malignancies. 71 …”

Section: Therapeutic Biomarkers Related To Oncogenic Pathways Inmentioning

confidence: 99%

Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies

2017

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Lymphoma is characterized by heterogeneous biology, pathologic features, and clinical outcome. This has been proven by accumulating pathologic and molecular evidence attributed to underlying aberrant alterations at genetic, epigenetic, transcriptional, protein, microenvironmental levels, and dysregulated oncogenic signaling pathways. In the era of precision medicine, targeting oncogenic pathways to design drugs and to optimize treatment regimens for the lymphoma patients is feasible and clinically significant. As such, further understanding of the biology and the mechanisms behind lymphoma development and identification of oncogenic pathway activation and pathway-based biomarkers to better design precise therapies are challenging but hopeful. Furthermore, pathway-based targeted therapies in combination with traditional chemotherapy, single specific targeted antibody therapy, and immunotherapy might raise the hope for the patients with lymphoma, especially for relapsed and refractory lymphoma patients.

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Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies

Abstract: Venetoclax has demonstrated promising results in relapsed/refractory lymphoid malignancies, with an acceptable adverse effect profile. As the role of BCL-2 inhibition in various malignancies becomes further elucidated, venetoclax may offer benefit to a myriad other patient populations.

Cited by 31 publications

References 33 publications

Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies

Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies

Frontline Treatment for Older Patients with Mantle Cell Lymphoma

Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies

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