Single-agent venetoclax was initially investigated in a phase II study including 58 patients with relapsed or refractory AML. It showed limited efficacy, with an overall response rate of 19%, and a short median response duration of 48 days. Notably, 4 of 12 patients with IDH1/2 mutations had a complete response. This led to the further development of biologically rationally designed combination strategies. The combination of venetoclax and azacitidine or decitabine was investigated in a phase Ib study including 145 elderly patients with previously untreated AML. Thrombocytopenia, neutropenia, and febrile neutropenia were the most common grade 3 or higher adverse events; the complete response rate was 77% and median overall survival was 18 months. The combination of venetoclax and low-dose cytarabine was investigated in a phase I/II study including older patients with previously untreated AML. This combination showed a similar toxicity profile to venetoclax and azacitidine, and among the 82% of patients who received the maxi mum tolerated dose of venetoclax, the complete response rate was 54% and median overall survival was 10 months. Based on these data, in 2018 the FDA approved the combination of venetoclax and azacitidine or decitabine or low-dose cytarabine for the initial treatment of AML in adults 75 years of age or older or who have comorbidities that preclude the use of intensive induction chemotherapy. A confirmatory phase III randomized trial has been recently published, with results further supporting use of this combination. In that study, 431 patients with previously untreated AML who were ineligible for standard chemotherapy were randomized to receive azacitidine alone or in combination with venetoclax. After a median follow-up of 21 months, patients treated with the combination had a significantly higher complete remission rate (37% vs 18%) and longer median overall survival (15 months vs 10 months), in spite of a higher rate of febrile neutropenia.

A list of published venetoclax-based combination studies is shown in Table 1. Multiple novel studies based on the above-outlined preclinical data are ongoing. These studies involve chemotherapy backbones, targeted agents, and immune oncology agents and may significantly improve the outcomes of patients affected by AML and other myeloid malignancies.

Table1. Outcomes in Clinical Trials of Venetoclax-Based Combinations in Acute Myeloid Leukemia

A deep understanding of apoptosis, a hallmark of cancer, has translated into the development of novel and effective biological agents for the treatment of hematological malignancies; a deeper knowledge of its interactions with other biological pathways is now contributing to the development of safer and more effective therapeutic strategies.

اخر الاخبار

اخبار العتبة العباسية المقدسة

سماحة السيد الصافي يكرم عددًا من عوائل الشهداء ضمن فعاليات مهرجان روح النبوة النسوي العالمي الثامن

إحدى أمهات الشهداء: نعتز بتضحيات أبنائنا ونفتخر بشهادتهم دفاعًا عن الدين والمقدسات

ضمن فعاليات مهرجان روح النبوة… عرض فيلم يوثق نشاطات الشعب النسوية في العتبة العباسية المقدسة

فعاليات مهرجان روح النبوة الثقافي تشهد تقديم أوبريت الثقلين القرآني

المزيد

الآخبار الصحية

ماذا يحدث لجسمك عند تناول الوجبات السريعة يوميا؟

لصحة عظام المرأة.. الشاي أفضل أم القهوة؟

لبناء العضلات وإنقاص الوزن.. ما أفضل توقيت لتناول البيض؟

أطعمة صحية تساعد على التعافي من "الإنفلونزا الخارقة"

المزيد

الآخبار التكنلوجية

دراسة تكشف قدرة الحيتان على سماع الأصوات منخفضة وعالية التردد من مسافة بعيدة

تجربة جديدة: الأسفلت المدعوم بالطحالب يقاوم الحفر ويقلل الانبعاثات الكربونية

تسريبات تكشف ملامح أول هاتف قابل للطي من "أبل"

رصد نوع نادر من القطط في تايلاند للمرة الأولى منذ عقود

المزيد

مواضيع ذات صلة

Application of Liquid Biopsy to Non-small- Cell Lung Cancer Lung

Circulating Tumor DNA

Biomarkers in the Blood and in Tissues: A Complementary Approach

Biomarkers in Oncology: An Evolving Concept

Clinical Development of Oblimersen for Acute Myeloid Leukemia

Modalities for treating cancer

Tumor markers

Proto-oncogenes

Cancer-Predisposing Genes

Stages of Carcinogenesis

Causative Factors in Human Cancer

Types of Tumors