Background and significance: There are typically high response rates to first line TKI therapies in chronic phase chronic myeloid leukemia (CP-CML). However, responses in later lines (second line and beyond) are diminished and highly dependent on the specific tyrosine kinase inhibitors (TKIs) used. Asciminib received FDA approval in October 2021 for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) CML-CP who were previously treated with two or more TKIs, and in patients with Ph+ CML-CP with the T315I mutation. Our goal in this study is to evaluate the role of asciminib therapy for patients with CML beyond clinical studies, in routine clinical practice.

Study Design and methods: Data for this study will be abstracted from the HJKC3 (H. Jean Khoury Cure CML Consortium) CML registry project (HJKC3-0005); the HJKC3 CML Registry is a collaborative academic multi-site registry. Patients will be consented to allow collection of both retrospective and prospective data for the HJKC3 CML Registry. The data forms and surveys will be built and managed through the Research Electronic Data Capture (REDCap), a secure web application managed by the Clinical & Translational Science Institute. Participating sites include members of the HJKC3 (curecml.org). This study will be an opportunity to evaluate asciminib usage in ‘real-world’ academic practices across the United States. This observational study will include cohorts of patients diagnosed with CP-CML previously treated with two or more tyrosine kinase inhibitors and/or receiving asciminib and/or those with a T315I mutation, not currently enrolled in a randomized controlled trial.

The HJKC3 CML Registry intends to collect clinical and patient reported outcome (PRO) data. After obtaining patient consent, patients will be invited to complete PRO assessments. The study will attempt to collect PRO data regardless of disease or treatment status. PRO assessments will be primarily administered online, though study staff will offer alternatives (e.g., phone) for participants without internet access. Study subjects will be emailed a link to access a secure platform hosted by one of the study sites, Medical College of Wisconsin (MCW), using the REDCap platform.

Study Objectives: The primary objective of the study is to describe characteristics of patients who were previously treated with two or more TKIs and treated with asciminib or with any other TKIs. The secondary objectives are to describe the clinical outcomes and PRO of those patients. Exploratory objectives include description of characteristics, treatment outcome and PRO for patients with T315I mutation.

Statistical plan: The sample size of approximately 225 participants during the 5-year recruitment period is based on the available clinical expertise and ongoing recruitment data in the HJKC3 CML registry in lieu of statistical power analysis. We estimate that 150 patients in the HJKC3 CML registry will be treated with other TKI and 75 treated with asciminib. Among a total of 225 patients, we estimate that 75 patients with the T315I mutation will be enrolled in the registry. No formal statistical inference will be drawn to compare the outcomes between these two groups. Bayesian predictive probability (PP) will be utilized for the exploratory analysis of Major Molecular Response (MMR). Survival probabilities will be computed using the Kaplan-Meier method, and the p-values from the log-rank test will be provided. Different PRO domains of the patient's symptoms and functioning will be analyzed separately (e.g., depression separate from fatigue, separate from GI symptoms, etc.) since combining them into a summary score may dilute the effects of the individual (and not necessarily related) components and mask actual change. The main objective for the analyses of PRO data from the registry is to describe any differences by treatment type in patients treated with asciminib and other TKIs.

Mauro:Pfizer: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Sun Pharma/SPARC: Research Funding. Atallah:BMS: Consultancy, Speakers Bureau; Abbvie: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Thompson:Bristol Myers Squibb: Research Funding; Novartis: Research Funding. Gao:Novartis: Research Funding; Takeda: Research Funding. Visotcky:Takeda: Research Funding; Novartis: Research Funding. Giever:Takeda: Research Funding; Novartis: Research Funding. Baim:Takeda: Research Funding; Novartis: Research Funding. Larson:Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Jamy:Ascentage: Other: Advisory Board Participation. Cortes:Abbvie: Consultancy, Research Funding; Forma Therapuetic: Consultancy; Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; Gilead: Consultancy. Druker:The RUNX1 Research Foundation: Membership on an entity's Board of Directors or advisory committees; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharma, Inc.: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Beat AML LLC: Membership on an entity's Board of Directors or advisory committees; Multicancer Early Detection (MCED) Consortium: Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Membership on an entity's Board of Directors or advisory committees; Therapy Architects, LLC: Membership on an entity's Board of Directors or advisory committees; CureOne: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: PI or Co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; AstraZeneca: Other: PI or Co-investigator on clinical trial(s) funded via contract with OHSU.; Enliven Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oregon Health & Science University: Current Employment, Patents & Royalties: #1518 (exclusive option agreement with CytoImage); #0606/Patent 6958335 (Novartis exclusive license); #2573; #0843; #0996; DNA SEQ: Membership on an entity's Board of Directors or advisory committees; Dana-Farber Cancer Institute: Patents & Royalties: #2063 (licensed exclusively to Merck & Co); and #2524, Research Funding; Bristol Myers Squibb: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Celgene: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Astellas: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Incyte: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Tolero: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Syndax: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Gilead: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; US Patent and Trademark Office: Patents & Royalties: Patents 6958335 (Novartis exclusive license), 4326534, 7416873, 7592142, 10473667, 10664967, 11049247; Recludix Pharma, Inc.: Consultancy, Current holder of stock options in a privately-held company; Labcorp: Membership on an entity's Board of Directors or advisory committees; Nemucore Medical Innovations, Inc.: Membership on an entity's Board of Directors or advisory committees; Iterion Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Cepheid: Membership on an entity's Board of Directors or advisory committees; Burroughs Wellcome Fund: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Biosciences: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Adela, Inc.: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Shah:Bristol Myers-Squibb Oncology: Research Funding. Pinilla-Ibarz:Takeda: Consultancy, Speakers Bureau; Secura Bio: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Lilly: Consultancy, Speakers Bureau. Ritchie:Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Other: Travel Support, Speakers Bureau; Novartis: Consultancy, Other: Travel Support, Research Funding, Speakers Bureau; Astellas Pharma, Jazz Pharmaceuticals, NS Pharma: Research Funding; Celgene, Incyte Corporation, Novartis: Consultancy; Ariad: Speakers Bureau; Pfizer: Consultancy, Other: travel, Research Funding. Rein:Incyte: Research Funding; Sumitomo Pharma: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; DAVA Oncology: Other: Speaker, travel ; CTI BioPharma: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprints Medicine: Research Funding; Cogent: Research Funding; Geron: Research Funding; Protagonist: Research Funding. Tantravahi:Novartis: Consultancy, Honoraria; Partnership for Health Analytic Research LLC: Consultancy, Honoraria; Karyopharm Therapeutics Inc: Consultancy, Honoraria, Research Funding; CTI BioPharma: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria. Smith:Servier: Consultancy.

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2023
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