TY - JOUR
T1 - Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia
AU - Konopleva, Marina
AU - Thirman, Michael J.
AU - Pratz, Keith W.
AU - Garcia, Jacqueline S.
AU - Recher, Christian
AU - Pullarkat, Vinod
AU - Kantarjian, Hagop M.
AU - DiNardo, Courtney D.
AU - Dail, Monique
AU - Duan, Yinghui
AU - Chyla, Brenda
AU - Potluri, Jalaja
AU - Miller, Catherine L.
AU - Wei, Andrew H.
N1 - Funding Information:
M. Konopleva reports other support from AbbVie during the conduct of the study as well as grants from AbbVie, Sanofi, Rafael Pharmaceutical, AstraZeneca, Ascent-age, Agios, Ablynx, Calithera, Cellectis, Eli Lilly, and Immunomet; other support from Genentech, Janssen, and Reata Pharmaceutical; and grants and other support from F. Hoffman La-Roche, Stemline Therapeutics, and Forty Seven outside the submitted work. M.J. Thirman reports grants from AbbVie during the conduct of the study as well as grants from Merck, Syndax, and TG Therapeutics and personal fees from AbbVie, Adaptive Biotechnologies, AstraZeneca, Celgene, Pharmacyclics, and Gen-entech outside the submitted work. K.W. Pratz reports grants and personal fees from AbbVie and Astellas during the conduct of the study as well as grants from Millennium and Agios and personal fees from BMS/Celgene, Jazz Pharmaceuticals, Novartis, and Boston Biomedical outside the submitted work. J.S. Garcia reports other support from AbbVie during the conduct of the study as well as personal fees from AbbVie; nonfinancial support and other support from Genentech; and other support from Prelude, AstraZeneca, and Pfizer outside the submitted work. C. Recher reports grants, personal fees, and nonfinancial support from AbbVie during the conduct of the study as well as grants and personal fees from Astellas; grants, personal fees, and nonfinancial support from BMS, Daiichi-Sankyo, Amgen, Jazz Pharmaceuticals, Novartis, and Roche; nonfinancial support from Gilead and Sanofi; personal fees from Janssen, Otsuka, Takeda, and Macrogenics; and grants from Agios and MaatPharma outside the submitted work. V. Pullarkat reports personal fees from AbbVie and Genentech outside the submitted work. H.M. Kantarjian reports research grants from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, Jazz, Novartis, and Pfizer and speakers bureau honoraria from AbbVie, Amgen, Aptitude Health, Ascentage, Astellas Health, AstraZeneca, Ipsen Pharmaceuticals, KAHRMe-dical Ltd, NOVA Research, Novartis, Pfizer, Precision Biosciences, and Taiho Pharmaceutical Canada. C.D. DiNardo reports personal fees from Astellas, Abb-Vie/Genentech, GSK, Novartis, Takeda, Kura, and Genmab; grants and personal fees from Agios/Servier, Celgene/BMS, ImmuneOnc and Foghorn; and nonfinancial support from Notable Labs outside the submitted work. M. Dail reports other support from Genentech/Roche during the conduct of the study as well as other support from Genentech/Roche outside the submitted work; in addition, M. Dail is an employee of
Publisher Copyright:
© 2022 The Authors.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Purpose: To evaluate efficacy andsafety of venetoclax+azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia. Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1- 28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates. Results: In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc; complete remission (CR) + CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) for FLT3-mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/ 8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/ 10.1 months. In patients treated with venetoclax + azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77% and median OS was 9.9 and 19.2 months, and in comutated FLT3-ITD + NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: When treated with venetoclax+ azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax + azacitidine in patients harboring FLT3-ITD.
AB - Purpose: To evaluate efficacy andsafety of venetoclax+azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia. Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1- 28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates. Results: In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc; complete remission (CR) + CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) for FLT3-mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/ 8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/ 10.1 months. In patients treated with venetoclax + azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77% and median OS was 9.9 and 19.2 months, and in comutated FLT3-ITD + NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: When treated with venetoclax+ azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax + azacitidine in patients harboring FLT3-ITD.
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U2 - 10.1158/1078-0432.CCR-21-3405
DO - 10.1158/1078-0432.CCR-21-3405
M3 - Article
C2 - 35063965
AN - SCOPUS:85129297862
SN - 1078-0432
VL - 28
SP - 2744
EP - 2752
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -