Chikumi 2022: Ivosidenib (Tibsovo, Servier Pharmaceuticals LLC) in combination with azacitidine has been approved by the Food and Drug Administration for newly diagnosed acute myeloid leukaemia (AML) in adults 75 years or older with a susceptible IDH1 mutation, as detected by an FDA-approved test, or who have comorbidities that prevent intensive induction chemotherapy.
The FDA granted approval based on the results of a randomised, multicenter, double-blind, placebo-controlled study (AG120-C-009, NCT03173248) that enrolled 146 patients with newly diagnosed AML with an IDH1 mutation who satisfied at least one of the following criteria: age 75 years or older, ECG performance status 2, significant cardiac or pulmonary disease, hepatic impairment with bilirubin > 1.5 times the upper limit of normal, creatinine clearance 45 mL/min, or other comorbidities On Days 1-28, patients were randomised 1:1 to receive ivosidenib 500 mg daily (N=72) or a matched placebo orally once daily (N=74) in combination with azacitidine 75 mg/m2/day on Days 1-7 or Days 1-5 and 8-9 of each 28-day cycle until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation
Kuvandudzwa mukupona-kusina chiitiko (EFS), kupona kwese (OS), uye chiyero uye nguva yekuregererwa kuzere zvakashandiswa kuona kushanda zvakanaka (CR). Nguva kubva ku randomization kusvika pakukundikana kwekurapa, kudzoka kubva pakuregererwa, kana kufa kubva kune chero chikonzero, chero chii chakauya pakutanga, chainzi EFS. Kukundikana kuwana CR mukati memavhiki e24 kwaionekwa sekukundikana kwekurapa. EFS yakaitika mu65 muzana yeavosidenib pamwe neazacitidine varwere uye 84 muzana ye placebo pamwe neazacitidine varwere (HR 0.35; 95 muzana CI: 0.17, 0.72, p=0.0038). Iyo yepakati OS mune ivosidenib pamwe neazacitidine ruoko yaive mwedzi 24.0 (95 muzana CI: 11.3, 34.1), nepo placebo plus azacitidine ruoko yaive mwedzi 7.9 (95 muzana CI: 4.1, 11.3) (HR 0.44; 95 muzana CI: 0.27, 0.73; p=0.0010). Chiyero cheCR muvosidenib pamwe neazacitidine ruoko chaive 47 muzana (95 muzana CI: 35 muzana, 59 muzana) uye 15 muzana (95 muzana CI: 8 muzana, 25 muzana) muchikamu che placebo pamwe neazacitidine ruoko. Nguva yepakati yeCR muivosidenib pamwe neazacitidine ruoko yakanga isingafungidzike (NE) (95 muzana yenguva yekuvimba: 13.0, NE) uye 11.2 mwedzi (95 muzana yekuvimba: 3.2, NE) mu placebo pamwe neazacitidine ruoko.
Manyoka, kuneta, kubuda ropa, kuda kurutsa, kurutsa, kuderera kwechido, leukocytosis, arthralgia, dyspnea, kurwadziwa kwemudumbu, mucositis, rash, electrocardiogram QT kureba, differentiation syndrome, uye myalgia ndizvo zvainyanya kuitika zvakaipa zveivosidenib pamwe chete neazacitidine kana semonotherapy. (25 muzana mune chero muedzo). Yambiro Yebhokisi pamirayiridzo yekuraira inoyambira vashandi vezvehutano nevarwere nezve mukana wekusiyaniswa kwechirwere, chinogona kuuraya kana kuuraya.
Ivosidenib inorayirwa pachiyero che 500 mg kamwe chete zuva rega rega, ine kana pasina chikafu, kusvikira kufambira mberi kwechirwere kana huturu husingagamuchirwi. PaMazuva 1-7 (kana Mazuva 1-5 uye 8-9) ega ega 28-zuva kutenderera, tanga kutungamirira ivosidenib pamwe chete neazacitidine 75 mg / m2 subcutaneously kana intravenously kamwe pazuva. Kurapa kunokurudzirwa kweisingasviki mwedzi mitanhatu kuvarwere vasina kufambira mberi kwehurwere kana kuti muchetura wakanyanya kupa nguva yekupindura kwekiriniki.
Wona ruzivo rwakazara rwekutemerwa kweTibsovo
