Relationship Between High Body Mass Index (BMI) and Treatment Outcomes in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Dasatinib or Imatinib: Retrospective Analysis of the Phase 3 DASISION Trial

Context In the treatment of CML-CP, early molecular responses to tyrosine kinase inhibitors (TKIs) are associated with improved long-term outcomes, and major molecular response (MMR) at 18 months is an important goal. Obesity may elevate the risk of CML (Strom 2009), and high BMI at diagnosis can delay time to response and reduce MMR rate in patients treated with first-line imatinib (Breccia 2013). In the phase 3 DASISION study (NCT00481247), dasatinib was associated with earlier, more durable, and deeper responses than imatinib (Cortes 2016). Objective Investigate the relationship between BMI and response to first-line TKIs. Design DASISION was an open-label multinational study assessing dasatinib versus imatinib for newly diagnosed CML-CP. Patients were randomized to 100mg dasatinib or 400mg imatinib once daily. In this exploratory analysis, patients were stratified according to high (≥25kg/m2) or normal BMI (<25kg/m2). Results Collectively, 259 patients received dasatinib (high BMI, n=109; normal BMI, n=147; unknown, n=3) and 260 received imatinib (high BMI, n=107; normal BMI, n=147; unknown, n=6). Baseline characteristics were balanced within BMI subgroups. High BMI subgroup: significant improvements for dasatinib versus imatinib in median time to MMR (9.2 vs 27.6 months; P<0.0001) and complete cytogenetic response (CCyR: 3.1 vs 6.1 months; P<0.0001), and in MMR (79.8 vs 59.8%; P=0.0004) and MR4-5 rates (54.1 vs 34.6%; P=0.0013). Normal BMI subgroup: numerical but non-significant benefits for dasatinib versus imatinib in median time to MMR (18.0 vs 21.5 months; P=0.4095) and CCyR (5.6 vs 6.0 months; P=0.1055), and in MMR (73.5 vs 67.3%; P=0.3335) and MR4-5 rates (36.7 vs 33.3%; P=0.6344). Dasatinib exposure was similar between BMI subgroups (imatinib data unavailable). Adverse events were comparable between BMI subgroups and were consistent with established safety profiles. Any-cause pleural effusion with dasatinib versus imatinib: high BMI, 34.3% vs 0%; normal BMI, 24.5% vs 2.0%. Conclusions Improved outcomes were seen in patients with high BMI treated with dasatinib versus imatinib; however, these differences were not seen with normal BMI. These findings need further validation to ascertain the role of BMI in predicting treatment responses in patients with CML-CP. Funding BMS. Previous presentation ASH 2019, HOPA 2020. In the treatment of CML-CP, early molecular responses to tyrosine kinase inhibitors (TKIs) are associated with improved long-term outcomes, and major molecular response (MMR) at 18 months is an important goal. Obesity may elevate the risk of CML (Strom 2009), and high BMI at diagnosis can delay time to response and reduce MMR rate in patients treated with first-line imatinib (Breccia 2013). In the phase 3 DASISION study (NCT00481247), dasatinib was associated with earlier, more durable, and deeper responses than imatinib (Cortes 2016). Investigate the relationship between BMI and response to first-line TKIs. DASISION was an open-label multinational study assessing dasatinib versus imatinib for newly diagnosed CML-CP. Patients were randomized to 100mg dasatinib or 400mg imatinib once daily. In this exploratory analysis, patients were stratified according to high (≥25kg/m2) or normal BMI (<25kg/m2). Collectively, 259 patients received dasatinib (high BMI, n=109; normal BMI, n=147; unknown, n=3) and 260 received imatinib (high BMI, n=107; normal BMI, n=147; unknown, n=6). Baseline characteristics were balanced within BMI subgroups. High BMI subgroup: significant improvements for dasatinib versus imatinib in median time to MMR (9.2 vs 27.6 months; P<0.0001) and complete cytogenetic response (CCyR: 3.1 vs 6.1 months; P<0.0001), and in MMR (79.8 vs 59.8%; P=0.0004) and MR4-5 rates (54.1 vs 34.6%; P=0.0013). Normal BMI subgroup: numerical but non-significant benefits for dasatinib versus imatinib in median time to MMR (18.0 vs 21.5 months; P=0.4095) and CCyR (5.6 vs 6.0 months; P=0.1055), and in MMR (73.5 vs 67.3%; P=0.3335) and MR4-5 rates (36.7 vs 33.3%; P=0.6344). Dasatinib exposure was similar between BMI subgroups (imatinib data unavailable). Adverse events were comparable between BMI subgroups and were consistent with established safety profiles. Any-cause pleural effusion with dasatinib versus imatinib: high BMI, 34.3% vs 0%; normal BMI, 24.5% vs 2.0%. Improved outcomes were seen in patients with high BMI treated with dasatinib versus imatinib; however, these differences were not seen with normal BMI. These findings need further validation to ascertain the role of BMI in predicting treatment responses in patients with CML-CP.