Title Venetoklakso ir IDH inhibitorių derinių klinikinis pritaikomumas gydant refrakterią/recidyvavusią ūminę mieloleukemiją su IDH 1/2 mutacijomis: atvejų analizė ir literatūros apžvalga /
Translation of Title Clinical applicability of venetoclax and idh inhibitor combinations in relapse/refractory idh-mutated acute myeloid leukaemia setting. literature review and case report.
Authors Achonen, Danielius
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Pages 42
Abstract [eng] Purpose: Ivosidenib and enasidenib, targeted IDH1/2 inhibitors, are used to treat IDH-mutated acute myeloid leukemia (AML). This thesis reviews recent clinical trial data on the safety and efficacy of combining these inhibitors with BCL-2 inhibitors and hypomethylating agents in treatment regimens. Additionally, it analyzes two clinical cases of patients treated with these therapies at Vilnius University Hospital Santaros Clinics, highlighting the applicability of these drugs in clinical practice. Methodology: Clinical trials on IDH-mutated AML published between 2015 and 2025 were identified using PubMed, Scopus, and Cochrane Library databases. Data were synthesized through thematic analysis and comparative tables, forming the literature review. A retrospective analysis of two clinical cases was conducted, detailing patient demographics, treatment regimens, and outcomes, presented in the case section. Results: The literature review identified key themes, including the efficacy of treatment regimens, with triplet therapies showing higher complete remission rates (up to 83%). Comparable patient groups were identified based disease stage (newly diagnosed or relapsed/refractory AML), and IDH mutation status, enabling a descriptive statistical comparison of outcomes while avoiding matched statistical analysis due to trial heterogeneity. The clinical cases illustrated the feasibility and challenges of implementing these therapies in a real clinical setting. Conclusion: The reviewed regimens, including IDH inhibitors in combinations with HMA and BCL-2 inhibitors, demonstrated comparable efficacy in relapsed/refractory AML, with complete remission (CR) rates of 40-60% in combination therapies versus 30–40% in IDH inhibitor monotherapy. For newly diagnosed AML patients with IDH1/2 mutations, triplet regimens showed superior efficacy, achieving CR rates up to 83%, though limited by small cohort sizes and trial heterogeneity. For newly diagnosed, unfit patients, low-dose cytarabine may serve as an alternative to hypomethylating agents in triplet regimens, warranting further investigation. Other emerging therapies e.g. ACTIVE based on the current status also show comparable efficiency and toxicity in R/R AML setting and is also prospected to further randomized trials.
Dissertation Institution Vilniaus universitetas.
Type Master thesis
Language Lithuanian
Publication date 2025