Leukemia research · 2023
Efficacy and tolerability of isocitrate dehydrogenase inhibitors in patients with acute myeloid leukemia: A systematic review of clinical trials.
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Aiman Wajeeha, Ali Muhammad Ashar, Basit Muhammad Abdul, Omar Zainab, Suleman Muhammad, Hassan Muhammad, Jamil Taimoor, Anwar Muhammad Saad, Shafique Zubair, Dhanesar Gurneel, Faisal Muhammad Salman, Akerman Michael J, Maroules Michael, Anwer Faiz
Аннотация
BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy due to anomalous differentiation and proliferation of hematopoietic stem cells with myeloid blast buildup. Induction chemotherapy is considered the first line of treatment in most patients with AML. However, targeted therapy in the form of FLT-3, IDH, BCL-2, and immune checkpoint inhibitors, can be considered as the first line depending on their molecular profile, resistance to chemotherapy, comorbidities, etc. This review aims to assess the tolerability and efficacy of isocitrate dehydrogenase (IDH) inhibitors in AML.
METHODS: We searched Medline, WOS, Embase, and clinicaltrials.gov. PRISMA guidelines were followed in this systematic review. 3327 articles were screened, and 9 clinical trials (N = 1119) were included.
RESULTS: In randomized clinical trials (RCTs), objective response (OR) was reported in 63-74% of the patients with IDH inhibitors + azacitidine as compared to 19-36 % of the patients with azacitidine monotherapy in newly diagnosed (ND) medically unfit patients. Survival rates were significantly improved with the use of ivosidenib. OR was reported in 39.1-46 % of the patients who relapsed/refractory to chemotherapy. ≥Grade 3 IDH differentiation syndrome and QT prolongation were reported in 3.9-10 % and 2-10 % of the patients, respectively.
CONCLUSION: IDH inhibitors (ivosidenib for IDH-1 and enasidenib for IDH-2) are safe and effective in treating ND medically unfit or relapsed refractory patients with IDH mutation. However, no survival benefit was reported with enasidenib. More randomized multicenter double-blinded clinical studies are needed to confirm these results and compare them with other targeting agents.
METHODS: We searched Medline, WOS, Embase, and clinicaltrials.gov. PRISMA guidelines were followed in this systematic review. 3327 articles were screened, and 9 clinical trials (N = 1119) were included.
RESULTS: In randomized clinical trials (RCTs), objective response (OR) was reported in 63-74% of the patients with IDH inhibitors + azacitidine as compared to 19-36 % of the patients with azacitidine monotherapy in newly diagnosed (ND) medically unfit patients. Survival rates were significantly improved with the use of ivosidenib. OR was reported in 39.1-46 % of the patients who relapsed/refractory to chemotherapy. ≥Grade 3 IDH differentiation syndrome and QT prolongation were reported in 3.9-10 % and 2-10 % of the patients, respectively.
CONCLUSION: IDH inhibitors (ivosidenib for IDH-1 and enasidenib for IDH-2) are safe and effective in treating ND medically unfit or relapsed refractory patients with IDH mutation. However, no survival benefit was reported with enasidenib. More randomized multicenter double-blinded clinical studies are needed to confirm these results and compare them with other targeting agents.