Background: First-line therapies for chronic-phase (CP) CML include the tyrosine kinase inhibitors(TKIs) dasatinib, nilotinib, bosutinib or imatinib, while ponatinib and asciminib are indicated only in later lines. There are typically high response rates to first-line therapy in CP-CML, with responses to second- and third-line therapy lower and highly dependent on the specific TKI. Our goal in this study is to evaluate the role of ponatinib in the treatment of patients with CML using data from routine clinical practice.
Study design and methods: Data will come from the H. Jean Khoury Cure CML Consortium (HJKC3) CML registry, a North American multi-site research database. Participating sites include the HJKC3 members (curecml.org). Patient inclusion criteria include a diagnosis CML in chronic phase, receiving second line therapy after initial therapy with a second generation TKI (dasatinib, nilotinib, or bosutinib) or receiving third or later line TKI therapy for CML. Participating patients provide consent to collect their data both retrospectively and prospectively for 1 year. Clinical data, including toxicities and complications of TKI therapy, are abstracted from the electronic health record. Participating patients are invited to complete a questionnaire to assess health-related quality of life. Data are managed using REDCap, a secure web application.
Study Objectives: The primary objective is to compare the outcome of patients treated with ponatinib vs. other TKIs as second or later line therapy. Secondary objectives are to evaluate patient-reported outcomes (PRO) for CML treated with second or later line therapy and to determine if there are any patient or disease characteristics that can predict outcomes.
Statistical plan for clinical outcomes: Descriptive statistics will be used to compare baseline demographic characteristics. Categorical variables will be compared using the Chi-square test. Continuous variables will be compared using ANOVA. Overall survival will be calculated from the time of diagnosis to death from any cause and patients will be censored if they were alive at the last follow-up. Survival probabilities will be computed using the Kaplan-Meier method and compared with the log-ranktest. Cox regression analyses will be used to determine significant factors that influence survival, and hazard ratios with 95% confidence intervals will be presented. Event free survival (EFS) and transformation free survival (TFS) will be calculated for patients. For EFS, loss of complete hematologic remission, loss of major cytogenetic response, progression to accelerated or blast phase, or death from any cause at any time will be considered an event. For TFS, transformation to accelerated or blast phase while on therapy or death on study will be considered an event.
Statistical plan for PRO: Different PRO domains will be analyzed separately (for example, depression separate from fatigue, etc.). Descriptive statistics for each PRO measure will be reported and compared to previously published studies. Differences by treatment type will be evaluated.
Disclosures
Thompson:Novartis: Research Funding; Bristol Myers Squibb: Research Funding. Gao:Takeda: Research Funding; Novartis: Research Funding. Visotcky:Novartis: Research Funding; Takeda: Research Funding. Mauro:Pfizer: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Sun Pharma/SPARC: Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel, accommodation, and expenses, Research Funding. Giever:Novartis: Research Funding; Takeda: Research Funding. Baim:Takeda: Research Funding; Novartis: Research Funding. Larson:AbbVie: Consultancy; Ariad/Takeda: Consultancy; Astellas: Consultancy, Research Funding; CVS/Caremark: Consultancy; Epizyme: Consultancy; Immunogen: Consultancy; Jazz Pharmaceuticals: Consultancy; Kling Biotherapeutics: Consultancy; MedPace: Consultancy; Novartis: Consultancy, Research Funding; Servier: Consultancy; Cellectis: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven/Gilead: Research Funding; Rafael Pharmaceuticals: Research Funding. Jamy:Ascentage: Other: Advisory Board Participation. Hunter:Sierra Oncology: Membership on an entity's Board of Directors or advisory committees. Kota:Pfizer: Honoraria; Incyte: Research Funding; Kite: Honoraria; Novartis: Honoraria. Cortes: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; Gilead: Consultancy; Takeda: Consultancy, Honoraria; Forma Therapuetic: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Druker:Aptose Biosciences: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; CureOne: 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; Aileron Therapeutics: 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; Dana-Farber Cancer Institute: Patents & Royalties: #2063 (licensed exclusively to Merck & Co); and #2524, Research Funding; DNA SEQ: Membership on an entity's Board of Directors or advisory committees; Labcorp: 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; Nemucore Medical Innovations, Inc.: Membership on an entity's Board of Directors or advisory committees; Recludix Pharma, Inc.: Consultancy, Current holder of stock options in a privately-held company; 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; 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.; Amgen: 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; Blueprint Medicines: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Syndax: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Burroughs Wellcome Fund: 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; Iterion Therapeutics: Current holder of stock options in a privately-held company, 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; Tolero: Other: Co-investigator on clinical trial(s) funded via contract with OHSU.; Adela, Inc.: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Gilead: Other: 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; 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.; Vincerx Pharma, Inc.: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; US Patent and Trademark Office: Patents & Royalties: Patents 6958335 (Novartis exclusive license), 4326534, 7416873, 7592142, 10473667, 10664967, 11049247; Oregon Health & Science University: Current Employment, Patents & Royalties: #1518 (exclusive option agreement with CytoImage); #0606/Patent 6958335 (Novartis exclusive license); #2573; #0843; #0996; AstraZeneca: Other: PI or Co-investigator on clinical trial(s) funded via contract with OHSU.. Shah:Bristol Myers-Squibb Oncology: Research Funding. Pinilla-Ibarz:Secura Bio: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Lilly: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Ritchie:Bristol Myers Squibb: Consultancy, Research Funding; Astellas Pharma, Jazz Pharmaceuticals, NS Pharma: Research Funding; Celgene, Incyte Corporation, Novartis: Consultancy; Pfizer: Consultancy, Other: travel, Research Funding; Celgene: Other: Travel Support, Speakers Bureau; Ariad: Speakers Bureau; Novartis: Consultancy, Other: Travel Support, Research Funding, Speakers Bureau. Rein:Sumitomo Pharma: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cogent: Research Funding; DAVA Oncology: Other: Speaker, travel ; CTI BioPharma: Consultancy; Blueprints Medicine: Research Funding; Incyte: Research Funding; Geron: Research Funding; Protagonist: Research Funding. Smith:Servier: Consultancy. Tantravahi:Incyte: Consultancy, Honoraria; Partnership for Health Analytic Research LLC: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; CTI BioPharma: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Karyopharm Therapeutics Inc: Consultancy, Honoraria, Research Funding. Deininger:Novartis, Takeda, Blueprint, Incyte, Dava Oncology, CTIBio, Syneos, Cogent, Pfizer, Dispersol: Consultancy. Atallah:Takeda: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding.
