Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm

Stéphane De Botton; Christian Récher; Jorge Cortes; Antonio Curti; Pierre Fenaux; Pierre Peterlin; Arnaud Pigneux; Karen Yee; Andrew Wei; Alice Mims; Gary Schiller; Mwe Mwe Chao; Hua Tian; Justin M Watts

doi:10.1111/bjh.19944

Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm

Br J Haematol. 2024 Dec 19. doi: 10.1111/bjh.19944. Online ahead of print.

Authors

Stéphane De Botton^{1

2}, Christian Récher³, Jorge Cortes⁴, Antonio Curti⁵, Pierre Fenaux⁶, Pierre Peterlin⁷, Arnaud Pigneux⁸, Karen Yee⁹, Andrew Wei¹⁰, Alice Mims¹¹, Gary Schiller¹², Mwe Mwe Chao¹³, Hua Tian¹³, Justin M Watts¹⁴

Affiliations

¹ Hematologie Clinique, Institut Gustave Roussy, Villejuif, France.
² Université Paris-Saclay, Villejuif, France.
³ Service d'hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France.
⁴ Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.
⁵ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology Seràgnoli, Bologna, Italy.
⁶ Département (DMU) d'hematologie et immunologie, APHP Nord, Service d'hématologie séniors, Hôpital St Louis/Université de Paris, Paris, France.
⁷ Nantes University Hospital, Nantes, France.
⁸ Bordeaux Haut-Leveque University Hospital, Pessac, France.
⁹ Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
¹¹ The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
¹² David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
¹³ Rigel Pharmaceuticals, Inc., South San Francisco, California, USA.
¹⁴ Division of Hematology, Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida, USA.

PMID: 39701584
DOI: 10.1111/bjh.19944

Abstract

Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small-molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post-MPN mIDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Primary end-points: safety and best response defined as complete remission (CR), CR with partial haematological recovery or morphological leukaemia-free state (MLFS). Analysis included 15 patients with post-MPN mIDH1 AML; 10 had relapsed or refractory AML and five had newly diagnosed AML. Six were treated with olutasidenib monotherapy and nine in combination with azacitidine. Treatment emergent adverse events occurred in 15 patients, three of whom discontinued therapy. CR: 40% (n = 6/15); median duration of response: 15.6 months (range: 1.7-44.3); CR with incomplete haematological recovery: 13% (n = 2/15); MLFS: 7% (n = 1/15); composite complete remission (CRc): 53% (n = 8/15); and overall response rate (ORR): 60% (9/18). Median duration of CRc and ORR: 13.15 (range: 2.4-48.7) and 14.3 months (range: 2.4-48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70-23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post-MPN mIDH1 AML.

Keywords: IDH1 mutation; acute myeloid leukaemia; blast‐phase myeloproliferative neoplasm; myeloproliferative neoplasms.

Abstract

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