Pb1966: The Effect of Body Mass Index on the Safety of Bosutinib in Patients With Chronic Myeloid Leukemia: A Post Hoc Pooled Data Analysis

Topic: 8. Chronic myeloid leukemia - Clinical Background: Bosutinib is approved for the treatment of Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and newly diagnosed Ph+ chronic phase (CP) CML1. Body mass index (BMI) has been shown to influence treatment response with frontline dasatinib vs imatinib2 and bosutinib vs imatinib3, as well as AE profiles3. Aims: To evaluate the effect of BMI on the safety of bosutinib in patients (pts) with previously treated or newly diagnosed CML. Methods: Safety data from seven trials with bosutinib were pooled for this post hoc analysis. Three studies included pts ≥18 years with previously treated CML: B1871006 (NCT00261846; phase 1/2), B1871007 (NCT00811070; phase 1/2 in Japanese pts), B1871039 (NCT02228382, BYOND; phase 4). Three studies included pts ≥18 years with newly diagnosed CML: B1871048 (NCT03128411, phase 2 in Japanese pts), B1871008 (NCT00574873, BELA; phase 3), B1871053 (NCT02130557, BFORE; phase 3). An extension study (B1871040, NCT01903733) included pts from B1871006 or B1871008. Bosutinib dose across the studies ranged from 100 mg to 600 mg once daily and study follow-up ranged from 28 days to 5 years. Safety outcomes were assessed according to baseline BMI <18.5, 18.5–<25, 25–<30, and ≥30 kg/m2. Results: A total of 1,333 pts were included in this safety analysis; 45 (3.4%), 582 (43.7%), 439 (32.9%) and 267 (20%) pts had BMI <18.5, 18.5–<25, 25–<30, and ≥30 kg/m2, respectively. The number of pts who reported treatment-emergent adverse events (TEAEs) was 44 (97.8%), 572 (98.3%), 437 (99.5%) and 266 (99.6%) for BMI <18.5, 18.5–<25, 25–<30, and ≥30 kg/m2, respectively. Dose interruptions due to TEAEs occurred in 30 (66.7%), 402 (69.1%), 315 (71.8%) and 195 (73%) pts with BMI <18.5, 18.5–<25, 25–<30, and ≥30 kg/m2, respectively. Dose reductions due to TEAEs occurred in 27 (60%), 301 (51.7%), 224 (51%) and 141 (52.8%) pts with BMI <18.5, 18.5–<25, 25–<30, and ≥30 kg/m2, respectively. The number of pts who discontinued treatment due to any AE was 10 (22.2%), 151 (25.9%), 128 (29.2%) and 82 (30.7%) for BMI groups <18.5, 18.5–<25, 25–<30, and ≥30 kg/m2, respectively. The most common AEs leading to treatment discontinuation were increased ALT for pts with BMI 18.5–<25 (3.3%), 25–<30 (4.6%), and ≥30 kg/m2 (4.1%), and thrombocytopenia for pts with BMI <18.5 (6.7%) and 18.5–<25 (3.3%). Grade 3/4 TEAEs that occurred in ≥5% of pts of any BMI group is shown in the Table. The most common grade 3/4 AEs occurring after 12 months of treatment were anemia (6.7%) and neutropenia (6.7%) in pts with BMI <18.5; lipase increased in pts with BMI 18.5–<25 (5.3%) and 25–<30 (5.9%), and lipase increased (5.2%) and hypertension (5.2%) in pts with BMI ≥30 kg/m2. Summary/Conclusion: The incidence of certain high grade TEAEs appeared to differ between BMI groups, with hematologic TEAEs appearing to be most common in patients with BMI <18.5 kg/m2.References 1.Brümmendorf, TH, et al. Leukemia 2022; 36(7):1825–1833 2.Breccia M, et al. Blood 2019;134(suppl 1):4155.2 3.Brümmendorf, TH, et al. Journal of Clinical Oncology 2021; 39(suppl 15):7037 Keywords: Safety, Chronic myeloid leukemia, Clinical trial