Changes in health-related quality of life in patients with newly diagnosed acute myeloid leukemia receiving ivosidenib + azacitidine or placebo + azacitidine.
Authors: Schuh Andre C. , De Botton Stéphane , Recher Christian , Vives Polo Susana , Zarzycka Ewa , Wang Jianxiang , Bertani Giambattista , Heuser Michael , Calado Rodrigo T. , Yeh Su-Peng , Hui Jianan , Pandya Shuchi Sumant , Gianolio Diego A. , Chamberlain Christina X. , Dohner Hartmut , Montesinos Pau 
Published: June 2022

e19024

Background: Ivosidenib (IVO) is a potent, targeted inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) that is approved for acute myeloid leukemia (AML). IVO plus azacitidine (AZA) demonstrated clinical benefit compared with placebo (PBO) and AZA in the AGILE study (NCT03173248), and here we report the impact of IVO+AZA versus PBO+AZA on health-related quality of life (HRQoL). Methods: In the double-blind, PBO-controlled phase 3 AGILE study, patients (pts) were randomized 1:1 to IVO 500 mg QD + AZA 75 mg/m2 SC or IV for 7 days in 28-day cycles, or PBO+AZA. HRQoL was a secondary endpoint assessed using two validated questionnaires: the European Organisation of Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L). Questionnaires were administered pre-dose on cycle (C) 1 Day (D) 1, on C1D15, C2D1, C2D15, and on D1 of every odd cycle thereafter until the end of treatment. Score change from baseline across visits for all subscales of EORTC QLQ-C30 was analyzed with mixed models. A 10-point threshold in EORTC QLQ-C30 subscale score was used to evaluate clinically meaningful changes from baseline or differences between arms. Two-sided nominal p-values are reported. Results: At baseline, 69 and 68 pts out of 72 receiving IVO+AZA completed the EORTC QLQ-C30 and EQ-5D-5L, respectively, and 66 pts out of 74 receiving PBO+AZA completed both. Mean baseline HRQoL scores were similar between treatment arms. There was an initial decline in HRQoL (EORTC QLQ-C30 global health status [GHS/QoL]) in both arms for ̃4 months, consistent with time to response, and which was generally not clinically meaningful. IVO+AZA was associated with preserved or improved HRQoL compared to baseline for most subscales of the EORTC QLQ-C30 from C5 to C19 (after which no PBO+AZA HRQoL data were available), and at most timepoints for EQ-5D-5L VAS scores and index values. EORTC QLQ-C30 subscales with clinically meaningful improvements from baseline at most timepoints from C5 to C19 in the IVO+AZA arm included GHS/QoL, fatigue, pain and appetite loss. In contrast, there were few clinically meaningful improvements from baseline in PBO+AZA pts. GHS/QoL scores were significantly improved (p≤0.05) for IVO+AZA versus PBO+AZA at C2D1, C2D15, C7 and C9, and differences were clinically meaningful at C2D1 (10.2 point difference), C2D15 (10.1), C7 (12.6), C9 (22.6), C13 (14.9), C15 (15.4) and C19 (19.2). Likewise, improvements in EORTC QLQ-C30 fatigue, appetite loss, nausea and vomiting, diarrhea, cognitive functioning and social functioning favored IVO+AZA over PBO+AZA at multiple timepoints. Conclusions: Data from the AGILE study show that patients with mIDH1 AML receiving treatment with IVO+AZA tended to report maintenance or improved HRQoL from cycle 5 through to cycle 19 compared with PBO+AZA. Clinical trial information: NCT03173248.