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1475 Efficacy and Safety of Bosutinib in Previously Treated Patients with Chronic Myeloid Leukemia: Final Results from the Byond Trial

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Trials, Adults, Clinical Research, Diseases, Myeloid Malignancies, Study Population
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Carlo Gambacorti-Passerini, MD1, Tim H Brümmendorf, MD2, Elisabetta Abruzzese, MD3, Kevin R. Kelly, MD, PhD4*, Vivian G. Oehler, MD5, Valentín Garcia-Gutiérrez, MD, PhD6, Henrik Hjorth-Hansen, MD7, Thomas Ernst, MD8, Eric Leip, PhD9*, Simon Purcell, MPharm10*, Gerald Luscan11*, Andrea Viqueira12*, Frank Giles, MD13* and Andreas Hochhaus, MD14

1University of Milan-Bicocca, Monza, Italy
2Universitätsklinikum RWTH Aachen, Aachen, Germany
3Hematology, S. Eugenio Hospital, Tor Vergata University, Rome, Italy
4Keck School of Medicine of USC, Los Angeles, CA
5Fred Hutchinson Cancer Research Ctr., Seattle, WA
6Hematology Service, Hospital Universitario Ramón y Cajal, Madrid, Spain
7Department of Hematology, St. Olavs University Hospital, Trondheim, Norway
8Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
9Pfizer Inc., Cambridge, MA
10Pfizer Ltd, London, GBR
11Pfizer PIO, Paris, France
12Pfizer SLU, Madrid, Spain
13Developmental Therapeutics Consortium, Chicago, IL
14Department of Internal Medicine II, Jena University Hospital, Jena, Germany

Introduction: Bosutinib is approved for patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and patients with newly diagnosed Ph+ chronic phase (CP) CML. The phase 4 BYOND trial (NCT02228382) further evaluated the efficacy and safety of bosutinib in patients with previously treated CML. We report the final results from BYOND.

Methods: Patients with CML resistant/intolerant to previous tyrosine kinase inhibitor therapy received bosutinib 500 mg once daily. This final analysis was based on a November 23, 2020 database lock, after 3 years of follow-up.

Results: Of 163 patients who received bosutinib, 156 had Ph+ CP CML; 4 patients with accelerated phase CML and 3 with Ph−/BCR-ABL1+ CML were analyzed separately. At study completion (median follow-up, 47.8 months), 48.1% of patient with Ph+ CP CML were still receiving treatment, and 68.6% completed the study. Most common primary reason for treatment discontinuation was adverse events (AEs) (26.9% [n=42/156]). Median treatment duration was 40.9 months (range, 0.2−50.1) and median dose intensity 306.4 mg/day (range, 79.7−560.6). Dose interruptions due to AEs occurred in 76.3% of patients and dose reductions in 79.5% of patients. Dose reduction (without further reduction) to 400, 300, or 200 mg/day occurred in 35 (22.4%), 46 (29.5%), and 38 (24.4%) patients, respectively.

In evaluable patients with Ph+ CP CML, 81.1% (95% CI: 73.7–87.2), 71.8% (95% CI: 63.9–78.9), 59.7% (95% CI: 51.4–67.7) and 48.3% (95% CI: 40.1−56.6) attained or maintained complete cytogenetic response, major molecular response (MMR), MR4, and MR4.5 respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib (Table 1). Among responders, the Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR4 at 36 months were 87.2% (78.0−92.7) and 80.7% (69.4−88.1), respectively. No patients with Ph+ CP CML progressed to accelerated/blast phase on-treatment. At 48 months, the cumulative incidence of progression free-survival events was 5.1% (95% CI: 2.4–9.4) and the Kaplan-Meier overall survival rate 88.3% (95% CI: 81.8–92.6). There were 17 deaths; 2 were considered CML-related (off-treatment progression to AP/BP, n=1; cardiogenic shock, n=1) and none were considered to be treatment-related by the investigator.

In the overall patient population (N=163), any grade treatment-emergent AEs (TEAEs) were reported by 99.4% of patients and grade 3/4 TEAEs were reported by 79.1% of patients (Table 2). Most common (≥10%) TEAEs leading to dose reduction were diarrhea (27.0%) and increased ALT (12.3%) and most common TEAEs leading to temporary dose interruption were diarrhea (30.7%), increased ALT (14.7%), vomiting (13.5%), increased AST (11.0%), and nausea (10.4%). AEs leading to treatment discontinuation in ≥2% of patients were increased ALT (4.9%) and AST (2.5%).

Conclusions: After 3 years, bosutinib continued to show efficacy in previously treated patients with Ph+ CP CML. Long-term AEs were generally manageable and consistent with previous reports of bosutinib. These results confirm the use of bosutinib as a standard of care in previously treated patients with CML.

Disclosures: Gambacorti-Passerini: Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Brümmendorf: Bristol Myers: Research Funding; Novartis: Honoraria, Patents & Royalties, Research Funding; Janssen: Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Repeat Diagnostics: Research Funding; Takepart Media: Honoraria. Abruzzese: Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Kelly: Gilead: Speakers Bureau; Karyopharm: Speakers Bureau; Pharmacyclics: Speakers Bureau; Epizyme: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; Janssen: Speakers Bureau; Bayer: Speakers Bureau; Agios: Current equity holder in publicly-traded company; Berkley Lights: Current equity holder in publicly-traded company; Amgen: Consultancy; Verastem: Consultancy; Denovo Biopharma: Consultancy; Sanofi-Aventis: Consultancy; AstraZeneca: Consultancy; Takeda: Consultancy; Bristol Myers Squibb: Honoraria. Oehler: OncLive: Honoraria; Takeda: Consultancy; Pfizer: Research Funding; BMS: Consultancy. Garcia-Gutiérrez: Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Incyte: Consultancy; Pfizer: Research Funding. Hjorth-Hansen: Pfizer: Research Funding; Novartis: Research Funding; AOP: Research Funding. Leip: Pfizer: Current Employment, Current equity holder in publicly-traded company. Purcell: Pfizer: Current Employment, Current equity holder in publicly-traded company. Luscan: Pfizer: Current Employment, Current equity holder in publicly-traded company. Viqueira: Pfizer: Current Employment, Current equity holder in publicly-traded company. Giles: Novartis: Consultancy; Actutate Therapeutics: Current Employment; Epigene Therapeutics: Consultancy, Current equity holder in publicly-traded company. Hochhaus: Pfizer: Research Funding; Incyte: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

*signifies non-member of ASH