Canadian real-world experience of asciminib treatment in heavily pre-treated chronic myeloid leukemia (CML) patients who failed multiple lines of tyrosine kinase inhibitor (TKI) therapy.


Journal

Leukemia research
ISSN: 1873-5835
Titre abrégé: Leuk Res
Pays: England
ID NLM: 7706787

Informations de publication

Date de publication:
10 2023
Historique:
received: 22 06 2023
revised: 16 08 2023
accepted: 21 08 2023
medline: 2 10 2023
pubmed: 2 9 2023
entrez: 1 9 2023
Statut: ppublish

Résumé

Asciminib is a novel drug specifically targeting ABL myristoyl pocket in the ABL1 protein. Forty one patients with chronic myeloid leukemia treated with asciminib from 2018 to 2022 were reviewed and analyzed for the efficacy and tolerability of asciminib using real-world experience data. The median age was 60 years (range 17-90) with a past history of a cardiovascular event in 21 patients (51%). Patients were pretreated with a median of 3 previous tyrosine kinase inhibitors (range 1-5). After a median of 12 months of asciminib (range 3-41), major molecular response (MMR) rate was 39% (n = 11/28) and 42% (n = 5/12) at 6 and 12 months, respectively. Molecular response with 2 log reduction (MR2) was noted in 54% (n = 15/28) and 50% (n = 6/12) at 6 and 12 months. The cumulative incidence of MMR and MR2 was 46.3% and 66% at 12 months. Five patients discontinued asciminib due to treatment failure (n = 3) or thrombocytopenia (n = 2). There were no cardiovascular events. Out of 7 patients treated with high dose asciminib for T315I mutation, 5 patients achieved MMR or deeper response. The event-free survival was 63% at 12 months. This study confirmed clinical efficacy and tolerability of asciminib with real-world experience.

Sections du résumé

BACKGROUND
Asciminib is a novel drug specifically targeting ABL myristoyl pocket in the ABL1 protein.
METHODS
Forty one patients with chronic myeloid leukemia treated with asciminib from 2018 to 2022 were reviewed and analyzed for the efficacy and tolerability of asciminib using real-world experience data.
RESULTS
The median age was 60 years (range 17-90) with a past history of a cardiovascular event in 21 patients (51%). Patients were pretreated with a median of 3 previous tyrosine kinase inhibitors (range 1-5). After a median of 12 months of asciminib (range 3-41), major molecular response (MMR) rate was 39% (n = 11/28) and 42% (n = 5/12) at 6 and 12 months, respectively. Molecular response with 2 log reduction (MR2) was noted in 54% (n = 15/28) and 50% (n = 6/12) at 6 and 12 months. The cumulative incidence of MMR and MR2 was 46.3% and 66% at 12 months. Five patients discontinued asciminib due to treatment failure (n = 3) or thrombocytopenia (n = 2). There were no cardiovascular events. Out of 7 patients treated with high dose asciminib for T315I mutation, 5 patients achieved MMR or deeper response. The event-free survival was 63% at 12 months.
CONCLUSION
This study confirmed clinical efficacy and tolerability of asciminib with real-world experience.

Identifiants

pubmed: 37657146
pii: S0145-2126(23)00639-2
doi: 10.1016/j.leukres.2023.107374
pii:
doi:

Substances chimiques

asciminib 0
Tyrosine Kinase Inhibitors 0
Protein Kinase Inhibitors 0
Fusion Proteins, bcr-abl EC 2.7.10.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107374

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest FK provides consultancy for Novartis, SC provides consultancy and has honoraria for Novartis, Pfizer, BMS, Celgene, Incite. AX, NF and LB has honoraria from Novartis. BL provides consultancy, has honoraria and on the advisory board for Novartis, Pfizer, BMS, Abbvie, and AMGEN. RK is on the advisory boards of Sanofi, FORUS Therapeutics, Belgene, Pfizer and has honoraria from Janssen and BMS. SA gets research funding from Novartis and has consultancy/ honoraria from Genentech/Roche, Astra Zeneca, Novartis, BMS, Jazz, Gilead, Amgen, Beigene, Abbvie, Paladin. DK is a consultant, has received research funding, and honoraria from Pfizer, Sanofi, Paladin, and Novartis. The remaining authors have no conflict of interest.

Auteurs

Fatima M Khadadah (FM)

Princess Margaret Cancer Centre, Toronto, ON, Canada.

Sonia Cerquozzi (S)

Tom Baker Cancer Centre, Calgary, AB, Canada.

Harold J Olney (HJ)

Department of Hematology, Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada.

Christina Fraga (C)

QEII Health Sciences, Halifax, NS, Canada.

Jill Dudebout (J)

Kingston General Hospital Center of Southeastern Ontario, Kingston, ON, Canada.

Anargyros Xenocostas (A)

Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada.

Nicholas Finn (N)

Centre Hospitalier Universitaire Dr. Georges-L.-Dumont, Moncton, NB, Canada.

Vincent Ethier (V)

Sherbrooke University Hospital Center, Sherbrooke, QC, Canada.

M Lynn Savoie (ML)

Tom Baker Cancer Centre, Calgary, AB, Canada.

Lambert Busque (L)

Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.

Kareem Jamani (K)

Tom Baker Cancer Centre, Calgary, AB, Canada.

Philip Kuruvilla (P)

The William Osler Health Center Brampton Civic Hospital, Brampton, ON, Canada.

Carolyn Faught (C)

The Ottawa Hospital, Ottawa, ON, Canada.

Brian Leber (B)

Department of Medicine, Division of Hematology, Juravinski Cancer Centre, Hamilton, ON, Canada.

Rayan Kaedbey (R)

Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Montreal, QC, Canada.

Sarit E Assouline (SE)

Department of Medicine and Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.

Dennis Kim (D)

Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address: dr.dennis.kim@uhn.ca.

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Classifications MeSH