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2152 Bosutinib for Previously Treated Patients with Philadelphia Chromosome-Positive Leukemia: ≥8-Year Update of a Phase 1/2 StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster II
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Tim H Brümmendorf, MD1, Jorge E. Cortes, MD2, Yeow Tee Goh, MBBS3, Musa Yilmaz, MD4, Rebecca B. Klisovic, MD5*, Simon Purcell6*, Andrea Viqueira7*, Eric Leip8* and Carlo Gambacorti-Passerini, MD9

1Universitätsklinikum RWTH Aachen, Aachen, Germany
2Georgia Cancer Center Augusta University, Augusta, GA
3Department of Hematology, Singapore General Hospital, Singapore, Singapore
4Department of Leukemia, MD Anderson Cancer Center, Houston, TX
5Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA
6Pfizer Ltd, London, GBR
7Pfizer SLU, Madrid, Spain
8Pfizer Inc., Cambridge, MA
9Dept of Medicine and Surgery, University of Milano Bicocca, Monza, MB, Italy

Introduction: Bosutinib is approved for use in patients with Philadelphia chromosome–positive (Ph+) chronic, accelerated or blast phase (CP, AP or BP) chronic myeloid leukemia (CML) that is resistant or intolerant to prior therapy, and in patients with newly diagnosed Ph+ CP CML.

Methods: A phase 1/2 study (NCT00261846) evaluated bosutinib at a starting dose of 500 mg/day in patients with CP CML resistant or intolerant to imatinib (CP2L), resistant or intolerant to imatinib + dasatinib and/or nilotinib (CP3L), or with AP/BP CML or Ph+ acute lymphoblastic leukemia with prior tyrosine kinase inhibitor (TKI) therapy (ADV). Here we report an ≥8-year update of this phase 1/2 study and its ongoing extension study (NCT01903733).

Results: Forty-one of 284 (14%) CP2L patients were still on bosutinib after ≥9 years and 8/119 (7%) CP3L and 4/167 (2%) ADV patients after ≥8 years. The most common reason for treatment discontinuation was disease progression/lack of efficacy in CP2L (27%), CP3L (42%) and ADV (50%) patients; the last dose before discontinuation was ≥500 mg/day in 70 (25%), 28 (24%) and 46 (28%) patients, respectively. Seventy-four CP2L patients discontinued bosutinib since Year 5 and 21 CP3L and 13 ADV patients since Year 4. In CP2L patients, median (range) follow-up was 54 (1–155) months, treatment duration 26 (<1–155) months and dose intensity 437 (87–599) mg/day; responses were durable (Table) and overall survival (OS; 95% CI) was 74% (67–80) at 9 years vs 84% (79–88) at 5 years. In CP3L and ADV patients, respectively, median (range) treatment duration was 9 (<1–148) and 4 (<1–147) months and dose intensity 427 (65–577) and 453 (26–594) mg/day. In CP3L, AP CML and BP CML patients, respectively, median (range) follow-up was 34 (<1–148), 29 (<1–147) and 10 (<1–131) months; OS (95% CI) was 69% (58–80), 55% (42–68) and 23% (7–38) at 8 years vs 78% (70–86), 59% (47–71) and 23% (7–38) at 4 years. Fifty-five CP2L, 29 CP3L and 98 ADV patients died on study (10, 3 and 2 since the 4/5-year reports); 15, 5 and 3 had on-treatment transformations to AP/BP (none since the 4/5-year reports). Across cohorts, the most common new treatment-emergent adverse events since Year 5 were pleural effusion (n=18), arthralgia (n=14), anemia (n=13), increased blood creatinine (n=13) and pneumonia (n=13).

Conclusions: Bosutinib demonstrated long-term efficacy and no new safety signals in patients with CML after ≥8 years, further supporting bosutinib use after prior TKIs.

Disclosures: Brümmendorf: Merck: Consultancy; Janssen: Consultancy; Novartis: Consultancy, Honoraria, Other: travel, accommodation, expenses, Patents & Royalties, Research Funding; Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Takeda: Consultancy. Cortes: Merus: Research Funding; Immunogen: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Amphivena Therapeutics: Research Funding; Astellas: Research Funding; Arog: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sun Pharma: Research Funding; Takeda: Consultancy, Research Funding; Telios: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; BiolineRx: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Yilmaz: Pfizer: Research Funding; Daicho Sankyo: Research Funding; Pint Pharma: Honoraria. Klisovic: Pfizer: Research Funding. Purcell: Pfizer: Current Employment, Current equity holder in publicly-traded company. Viqueira: Pfizer: Current Employment, Current equity holder in publicly-traded company. Leip: Pfizer: Current Employment, Current equity holder in publicly-traded company. Gambacorti-Passerini: Bristol-Myers Squibb: Consultancy; Pfizer: Honoraria, Research Funding.

*signifies non-member of ASH