Functional cure with single agent olutasidenib in relapsed IDH1/NPM1 co-mutated AML

被引：0

作者：

Watts, Justin ^{[1
]}

Nong, Tiffany ^{[1
]}

Micin, Katarina ^{[1
]}

Soong, Deborah ^{[1
]}

Madarang, Ellen ^{[2
]}

Affer, Maurizio ^{[1
]}

Mehra, Shefali ^{[1
]}

Lesmes, Jessica Alvarez ^{[3
]}

Chapman, Jennifer ^{[3
]}

Zhou, Yi ^{[3
]}

Thomassen, Amber ^{[1
]}

Bradley, Terrence ^{[1
]}

Totiger, Tulasigeri ^{[1
]}

Swords, Ronan ^{[4
]}

Taylor, Justin ^{[1
]}

机构：

[1] Univ Miami, Sylvester Comprehens Canc Ctr, Div Hematol, Miami, FL 33146 USA

[2] Univ Miami, Sylvester Comprehens Canc Ctr, Dept Pharm, Miami, FL USA

[3] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL USA

[4] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol Med Oncol, Portland, OR USA

来源：

NPJ PRECISION ONCOLOGY | 2025年 / 9卷 / 01期

关键词：

ACUTE MYELOID-LEUKEMIA; MUTATIONS; IDH1; CLASSIFICATION; PROGNOSIS; RELEVANCE; ADULTS;

D O I：

10.1038/s41698-025-01013-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Olutasidenib is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that was recently approved by the US FDA for adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring mutant IDH1. In the pivotal Phase II trial of olutasidenib, the median duration of complete response (CR) was 28.1 months. Here we report the first patient in the world to receive olutasidenib, for relapsed NPM1 and IDH1 co-mutated AML, who remains in continuous CR for over 7 years on olutasidenib monotherapy. We detail the clinical course as well as the pathologic and genomic evolution of the disease. Furthermore, using a novel single cell measurable residual disease assay and digital PCR and qPCR for the detection of IDH1 and NPM1 mutations, we found no evidence of residual detectable leukemia. To our knowledge, this is the first report of an AML patient functionally cured by IDH1 inhibitor monotherapy.

引用

页数：6

共 38 条

[1]

[Anonymous], 2023, Cancer Stat Facts: Leukemia-Acute Myeloid Leukemia (AML): National Cancer Institute Surveillance, Epidemiology, and End Results Program

[2] Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia:: results from Cancer and Leukemia Group B (CALGB 8461) [J].

Byrd, JC ;

Mrózek, K ;

Dodge, RK ;

Carroll, AJ ;

Edwards, CG ;

Arthur, DC ;

Pettenati, MJ ;

Patil, SR ;

Rao, KW ;

Watson, MS ;

Koduru, PRK ;

Moore, JO ;

Stone, RM ;

Mayer, RJ ;

Feldman, EJ ;

Davey, FR ;

Schiffer, CA ;

Larson, RA ;

Bloomfield, CD .

BLOOD, 2002, 100 (13) :4325-4336

[3] Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor [J].

Caravella, Justin A. ;

Lin, Jian ;

Diebold, R. Bruce ;

Campbell, Ann-Marie ;

Ericsson, Anna ;

Gustafson, Gary ;

Wang, Zhongguo ;

Castro, Jennifer ;

Clarke, Andrea ;

Gotur, Deepali ;

Josephine, Helen R. ;

Katz, Marie ;

Kershaw, Mark ;

Yao, Lili ;

Toms, Angela, V ;

Barr, Kenneth J. ;

Dinsmore, Christopher J. ;

Walker, Duncan ;

Ashwell, Susan ;

Lu, Wei .

JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (04) :1612-1623

[4] Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML [J].

Choe, Sung ;

Wang, Hongfang ;

DiNardo, Courtney D. ;

Stein, Eytan M. ;

de Botton, Stephane ;

Roboz, Gail J. ;

Altman, Jessica K. ;

Mims, Alice S. ;

Watts, Justin M. ;

Pollyea, Daniel A. ;

Fathi, Amir T. ;

Tallman, Martin S. ;

Kantarjian, Hagop M. ;

Stone, Richard M. ;

Quek, Lynn ;

Konteatis, Zenon ;

Dang, Lenny ;

Nicolay, Brandon ;

Nejad, Parham ;

Liu, Guowen ;

Zhang, Vickie ;

Liu, Hua ;

Goldwasser, Meredith ;

Liu, Wei ;

Marks, Kevin ;

Bowden, Chris ;

Biller, Scott A. ;

Attar, Eyal C. ;

Wu, Bin .

BLOOD ADVANCES, 2020, 4 (09) :1894-1905

[5]

Cortes JE, 2024, J CLIN ONCOL, V42

[6] Cancer-associated IDH1 mutations produce 2-hydroxyglutarate [J].

Dang, Lenny ;

White, David W. ;

Gross, Stefan ;

Bennett, Bryson D. ;

Bittinger, Mark A. ;

Driggers, Edward M. ;

Fantin, Valeria R. ;

Jang, Hyun Gyung ;

Jin, Shengfang ;

Keenan, Marie C. ;

Marks, Kevin M. ;

Prins, Robert M. ;

Ward, Patrick S. ;

Yen, Katharine E. ;

Liau, Linda M. ;

Rabinowitz, Joshua D. ;

Cantley, Lewis C. ;

Thompson, Craig B. ;

Heiden, Matthew G. Vander ;

Su, Shinsan M. .

NATURE, 2009, 462 (7274) :739-U52

[7] Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML [J].

de Botton, Stephane ;

Fenaux, Pierre ;

Yee, Karen ;

Recher, Christian ;

Wei, Andrew H. ;

Montesinos, Pau ;

Taussig, David C. ;

Pigneux, Arnaud ;

Braun, Thorsten ;

Curti, Antonio ;

Grove, Carolyn ;

Jonas, Brian A. ;

Khwaja, Asim ;

Legrand, Ollivier ;

Peterlin, Pierre ;

Arnan, Montserrat ;

Blum, William ;

Cilloni, Daniela ;

Hiwase, Devendra K. ;

Jurcic, Joseph G. ;

Krauter, Juergen ;

Thomas, Xavier ;

Watts, Justin M. ;

Yang, Jay ;

Polyanskaya, Olga ;

Brevard, Julie ;

Sweeney, Jennifer ;

Barrett, Emma ;

Cortes, Jorge .

BLOOD ADVANCES, 2023, 7 (13) :3117-3127

[8] Molecular Characteristics of Response to Olutasidenib (FT-2102) in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia [J].

De Botton, Stephane ;

Yee, Karen ;

Recher, Christian ;

Wei, Andrew H. ;

Montesinos, Pau ;

Taussig, David ;

Pigneux, Arnaud ;

Braun, Thorsten ;

Curti, Antonio ;

Esteve, Jordi ;

Grove, Carolyn ;

Jonas, Brian A. ;

Khwaja, Asim ;

Legrand, Olivier ;

Peterlin, Pierre ;

Sangerman, Montserrat Arnan ;

Blum, William G. ;

Cilloni, Daniela ;

Hiwase, Devendra ;

Jurcic, Joseph G. ;

Krauter, Jurgen ;

Thomas, Xavier ;

Watts, Justin ;

Yang, Jay ;

Xin, Zihao ;

Sedkov, Alex ;

Guichard, Sylvie ;

Sweeney, Jennifer ;

Marzac, Christophe ;

Cortes, Jorge E. ;

Fenaux, Pierre .

BLOOD, 2021, 138

[9] Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML [J].

DiNardo, C. D. ;

Stein, E. M. ;

de Botton, S. ;

Roboz, G. J. ;

Altman, J. K. ;

Mims, A. S. ;

Swords, R. ;

Collins, R. H. ;

Mannis, G. N. ;

Pollyea, D. A. ;

Donnellan, W. ;

Fathi, A. T. ;

Pigneux, A. ;

Erba, H. P. ;

Prince, G. T. ;

Stein, A. S. ;

Uy, G. L. ;

Foran, J. M. ;

Traer, E. ;

Stuart, R. K. ;

Arellano, M. L. ;

Slack, J. L. ;

Sekeres, M. A. ;

Willekens, C. ;

Choe, S. ;

Wang, H. ;

Zhang, V. ;

Yen, K. E. ;

Kapsalis, S. M. ;

Yang, H. ;

Dai, D. ;

Fan, B. ;

Goldwasser, M. ;

Liu, H. ;

Agresta, S. ;

Wu, B. ;

Attar, E. C. ;

Tallman, M. S. ;

Stone, R. M. ;

Kantarjian, H. M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (25) :2386-2398

[10] Interactions and relevance of blast percentage and treatment strategy among younger and older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [J].

DiNardo, Courtney D. ;

Garcia-Manero, Guillermo ;

Pierce, Sherry ;

Nazha, Aziz ;

Bueso-Ramos, Carlos ;

Jabbour, Elias ;

Ravandi, Farhad ;

Cortes, Jorge ;

Kantarjian, Hagop .

AMERICAN JOURNAL OF HEMATOLOGY, 2016, 91 (02) :227-232

← 1 2 3 4 →