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Patient-reported outcomes in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia receiving standard chemotherapy plus quizartinib or placebo (QuANTUM-First): a global, randomised, placebo-controlled, phase 3 trial
Background
QuANTUM-First is a randomised phase 3 trial in individuals with newly diagnosed acute myeloid leukaemia (AML) that is FLT3 internal tandem duplication (ITD) positive, showing a survival advantage for quizartinib versus placebo plus standard induction and consolidation chemotherapy with or without transplantation, followed by single-agent maintenance therapy. We evaluated the impact of quizartinib on patient-reported outcomes and health-related quality of life using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire.
In this global, multicentre, randomised, placebo-controlled, phase 3 trial, we recruited adults aged 18-75 years, with FLT3-ITD-positive newly diagnosed AML or AML secondary to myelodysplastic syndrome or myeloproliferative neoplasm, and with an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly allocated (1:1) to quizartinib (40 mg/day) or placebo plus standard 7 + 3 induction chemotherapy, and then received standard consolidation chemotherapy with high-dose cytarabine plus quizartinib (40 mg/day) or placebo, allogeneic haematopoietic cell transplantation (allo-HCT), or both, followed by maintenance with single-agent quizartinib (30-60 mg/day) or placebo for up to 36 cycles. Randomisation was managed via an interactive web and voice response system. Patient-reported outcome endpoints, assessed using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, were exploratory and analyses were based on the patient-reported outcome intention-to-treat analysis set. Treatment effects on patient-reported outcomes were assessed using the mixed-effects model for repeated measures, time to sustained improvement, and time until definitive deterioration analyses. A minimal clinically important difference score of 10 or higher for each subscale was defined as clinically meaningful. This trial is registered with ClinicalTrials.gov, NCT02668653, and is completed.
Findings
Participants were enrolled between Sept 27, 2016, and Aug 14, 2019. Of 539 randomly allocated participants, 509 (278 [55%] female and 231 [45%] male) were included in the patient-reported outcome analysis set, 254 in the quizartinib group and 255 in the placebo group. The overall median follow-up was 39·2 months (IQR 31·9-45·8). Baseline patient-reported outcome scores were similar between groups. The change in global health status and quality of life score (GHS-QoL) from baseline was above the minimal clinically important difference from consolidation onwards in both groups. The treatment difference (quizartinib minus placebo) in change from baseline for GHS-QoL (by mixed-effects model for repeated measures) was -2·0 (95% CI -4·8 to 0·7, nominal p=0·15), indicating no substantial difference between groups, further confirmed by time to sustained improvement (subdistribution hazard ratio [SHR] 1·126 [95% CI 0·904 to 1·403], nominal p=0·28) and time until definitive deterioration (hazard ratio 0·81 [95% CI 0·51 to 1·28], nominal p=0·37) analyses. Longitudinal analyses of the functional and symptom subscales showed no substantially different patterns between groups. For the functional subscales, the SHR ranged from 0·940 to 1·148 (0·737-1·544, nominal p=0·36-0·90). For the symptom subscales, the SHR ranged from 0·965 to 1·407 (0·720-1·989, nominal p=0·28-0·99).
Interpretation
The results indicate that quizartinib plus standard chemotherapy prolongs overall survival without adversely affecting patient-reported outcomes and health-related quality of life, with no substantial differences between groups. Future research in real-world settings is warranted to assess the generalisability of these patient-reported outcome results.
Authors
E N Olíva, F Cottone, S Unni, A Correges, J B Hansen, X L Marston, J Cortes, M A Sekeres
Journal
The Lancet Haematology
Therapeutic Area
Oncology
Center of Excellence
Real-world Evidence & Data Analytics
Year
2026
Read full article
In this global, multicentre, randomised, placebo-controlled, phase 3 trial, we recruited adults aged 18-75 years, with FLT3-ITD-positive newly diagnosed AML or AML secondary to myelodysplastic syndrome or myeloproliferative neoplasm, and with an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly allocated (1:1) to quizartinib (40 mg/day) or placebo plus standard 7 + 3 induction chemotherapy, and then received standard consolidation chemotherapy with high-dose cytarabine plus quizartinib (40 mg/day) or placebo, allogeneic haematopoietic cell transplantation (allo-HCT), or both, followed by maintenance with single-agent quizartinib (30-60 mg/day) or placebo for up to 36 cycles. Randomisation was managed via an interactive web and voice response system. Patient-reported outcome endpoints, assessed using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, were exploratory and analyses were based on the patient-reported outcome intention-to-treat analysis set. Treatment effects on patient-reported outcomes were assessed using the mixed-effects model for repeated measures, time to sustained improvement, and time until definitive deterioration analyses. A minimal clinically important difference score of 10 or higher for each subscale was defined as clinically meaningful. This trial is registered with ClinicalTrials.gov, NCT02668653, and is completed.
Findings
Participants were enrolled between Sept 27, 2016, and Aug 14, 2019. Of 539 randomly allocated participants, 509 (278 [55%] female and 231 [45%] male) were included in the patient-reported outcome analysis set, 254 in the quizartinib group and 255 in the placebo group. The overall median follow-up was 39·2 months (IQR 31·9-45·8). Baseline patient-reported outcome scores were similar between groups. The change in global health status and quality of life score (GHS-QoL) from baseline was above the minimal clinically important difference from consolidation onwards in both groups. The treatment difference (quizartinib minus placebo) in change from baseline for GHS-QoL (by mixed-effects model for repeated measures) was -2·0 (95% CI -4·8 to 0·7, nominal p=0·15), indicating no substantial difference between groups, further confirmed by time to sustained improvement (subdistribution hazard ratio [SHR] 1·126 [95% CI 0·904 to 1·403], nominal p=0·28) and time until definitive deterioration (hazard ratio 0·81 [95% CI 0·51 to 1·28], nominal p=0·37) analyses. Longitudinal analyses of the functional and symptom subscales showed no substantially different patterns between groups. For the functional subscales, the SHR ranged from 0·940 to 1·148 (0·737-1·544, nominal p=0·36-0·90). For the symptom subscales, the SHR ranged from 0·965 to 1·407 (0·720-1·989, nominal p=0·28-0·99).
Interpretation
The results indicate that quizartinib plus standard chemotherapy prolongs overall survival without adversely affecting patient-reported outcomes and health-related quality of life, with no substantial differences between groups. Future research in real-world settings is warranted to assess the generalisability of these patient-reported outcome results.
Authors
E N Olíva, F Cottone, S Unni, A Correges, J B Hansen, X L Marston, J Cortes, M A Sekeres
Journal
The Lancet Haematology
Therapeutic Area
Oncology
Center of Excellence
Real-world Evidence & Data Analytics
Year
2026
Read full article