The pivotal RATIFY study demonstrated midostaurin (50 mg twice daily) with standard chemotherapy significantly reduced mortality in adult patients (<60 years) with newly diagnosed (ND) FLT3(mut) acute myeloid leukemia (AML). Considering that AML often present in older patients who show poor response to chemotherapy, this open-label, multicenter phase 3b trial was designed to further assess safety and efficacy of midostaurin plus chemotherapy in induction, consolidation, and maintenance monotherapy in young (<= 60 years) and older (>60 years) patients with FLT3(mut) ND-AML. Compared with RATIFY, this study extended midostaurin treatment from 14 days to 21 days, substituted anthracyclines (idarubicin or daunorubicin), and introduced variation in standard combination chemotherapy dosing ("7+3" or "5+2" in more fragile patients). Total 301 patients (47.2% >60 years and 82.7% with FLT3-ITDmut) of median age 59 years entered induction phase. Overall, 295 patients (98.0%) had at least 1 adverse event (AE), including 254 patients (84.4%) with grade >= 3 AE. The grade >= 3 serious AEs occurred in 134 patients. No difference was seen in AE frequency between age groups, but grade >= 3AE frequency was higher in older patients. Overall, complete remission (CR) rate including incomplete hematologic recovery (CR + CRi) (80.7% [95% confidence interval, 75.74-84.98]) was comparable between age groups (<= 60 years [83.5%]; >60 to <= 70 years [82.5%]; in patients >70 years [64.1%]) and the type of anthracycline used in induction. CR + CRi rate was lower in males (76.4%) than females (84.4%). Overall, the safety and efficacy of midostaurin remains consistent with previous findings, regardless of age, sex, or induction regimen. The trial is registered at www.clinicaltrials.gov as #NCT03379727.

Midostaurin plus daunorubicin or idarubicin for young and older adults with FLT3-mutated AML: a phase 3b trial / Sierra, J.; Montesinos, P.; Thomas, X.; Griskevicius, L.; Cluzeau, T.; Caillot, D.; Legrand, O.; Minotti, C.; Luppi, M.; Farkas, F.; Bengoudifa, B. R.; Gilotti, G.; Hodzic, S.; Rambaldi, A.; Venditti, A.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 7:21(2023), pp. 6441-6450. [10.1182/bloodadvances.2023009847]

Midostaurin plus daunorubicin or idarubicin for young and older adults with FLT3-mutated AML: a phase 3b trial

Minotti C.;Luppi M.;
2023

Abstract

The pivotal RATIFY study demonstrated midostaurin (50 mg twice daily) with standard chemotherapy significantly reduced mortality in adult patients (<60 years) with newly diagnosed (ND) FLT3(mut) acute myeloid leukemia (AML). Considering that AML often present in older patients who show poor response to chemotherapy, this open-label, multicenter phase 3b trial was designed to further assess safety and efficacy of midostaurin plus chemotherapy in induction, consolidation, and maintenance monotherapy in young (<= 60 years) and older (>60 years) patients with FLT3(mut) ND-AML. Compared with RATIFY, this study extended midostaurin treatment from 14 days to 21 days, substituted anthracyclines (idarubicin or daunorubicin), and introduced variation in standard combination chemotherapy dosing ("7+3" or "5+2" in more fragile patients). Total 301 patients (47.2% >60 years and 82.7% with FLT3-ITDmut) of median age 59 years entered induction phase. Overall, 295 patients (98.0%) had at least 1 adverse event (AE), including 254 patients (84.4%) with grade >= 3 AE. The grade >= 3 serious AEs occurred in 134 patients. No difference was seen in AE frequency between age groups, but grade >= 3AE frequency was higher in older patients. Overall, complete remission (CR) rate including incomplete hematologic recovery (CR + CRi) (80.7% [95% confidence interval, 75.74-84.98]) was comparable between age groups (<= 60 years [83.5%]; >60 to <= 70 years [82.5%]; in patients >70 years [64.1%]) and the type of anthracycline used in induction. CR + CRi rate was lower in males (76.4%) than females (84.4%). Overall, the safety and efficacy of midostaurin remains consistent with previous findings, regardless of age, sex, or induction regimen. The trial is registered at www.clinicaltrials.gov as #NCT03379727.
2023
7
21
6441
6450
Midostaurin plus daunorubicin or idarubicin for young and older adults with FLT3-mutated AML: a phase 3b trial / Sierra, J.; Montesinos, P.; Thomas, X.; Griskevicius, L.; Cluzeau, T.; Caillot, D.; Legrand, O.; Minotti, C.; Luppi, M.; Farkas, F.; Bengoudifa, B. R.; Gilotti, G.; Hodzic, S.; Rambaldi, A.; Venditti, A.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 7:21(2023), pp. 6441-6450. [10.1182/bloodadvances.2023009847]
Sierra, J.; Montesinos, P.; Thomas, X.; Griskevicius, L.; Cluzeau, T.; Caillot, D.; Legrand, O.; Minotti, C.; Luppi, M.; Farkas, F.; Bengoudifa, B. R.; Gilotti, G.; Hodzic, S.; Rambaldi, A.; Venditti, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1332635
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