Discussion
pleural effusion, comorbidity, gastrointestinal TEAEs, edema, toxicities, TEAEs, Comorbidity, myelosuppression, effusion
CHRONIC MYELOID LEUKEMIA, PLEURAL EFFUSION, EDEMA, EVENT, CML, EFFUSION, EVENTS
After ≥3 years of follow-up in the phase 4 BYOND study, a substantial proportion of patients across age and mCCI groups achieved/maintained cytogenetic and molecular responses. Cumulative CCyR and MMR rates were comparable in patients across age groups. Older patients (≥75 years) and those with high comorbidity burden (mCCI ≥4) had higher rates of grade 3/4 and serious TEAEs. There was a trend toward higher rates of treatment discontinuation due to AEs with increasing age and in those patients with a high comorbidity burden. Across age and mCCI groups, dose reductions and interruptions were frequently used to manage AEs. Dose reduction to 400, 300, or 200 mg QD to manage TEAEs did not have an impact on efficacy in any subgroup. This is consistent with a previous study of bosutinib in patients with CP CML resistant/intolerant to prior therapy, which demonstrated that dose reduction did not compromise efficacy while reducing the occurrence of some common TEAEs, such as gastrointestinal TEAEs, even at doses as low as bosutinib 200 mg QD [As expected in patients receiving TKIs, the estimated OS rate at 48 months was high (>68%) in each subgroup [Patients with a medical history of liver, myelosuppression, edema, renal, effusion, cardiac, and vascular cluster events were more likely to experience the corresponding TEAE event of interest than those patients without the relevant medical history. Therefore, proactive management and monitoring may be warranted in patients with these preexisting conditions. These results are generally consistent with what has previously been reported for bosutinib treatment [Health-related quality of life was maintained from baseline throughout treatment for patients aged <65 and 65–74 years and patients with mCCI 2. A meaningful reduction in health-related quality of life was seen at multiple timepoints on treatment in patients aged ≥75 years, and patients with mCCI 3 and 4. A potential reason for this is that the increase in grade 3–4 and serious TEAEs observed in these subgroups of patients adversely affected health-related quality of life, as has been previously reported in patients receiving TKIs [Together these results suggest that while a substantial proportion of patients maintained/achieved cytogenetic and molecular responses with bosutinib across age groups and mCCI scores, both comorbidities and age are important factors to consider during bosutinib treatment. Older patients and those with a high comorbidity burden are more likely to experience more severe TEAEs, which can also impact health-related quality of life. Age, comorbidities, and risk factors, as well as the safety profile and schedule of administration of TKIs, should be considered when selecting the most appropriate TKI for the treatment of patients with previously treated CML. Patients should be monitored throughout treatment, not only for response but also for health conditions, whether they were preexisting or developed during therapy [The phase 2 Bosutinib in Elderly Chronic Myeloid Leukemia (BEST) and Bosutinib Dose Optimization (BODO) studies investigated dose optimization strategies to minimize the severity and incidence of AEs [Although comparisons between studies are difficult due to differences in methodologies and patient populations, the results reported here for bosutinib appear comparable to those with other second-generation TKIs. In a retrospective study of patients with resistance or intolerance to imatinib who received dasatinib, stratification by Charlson Comorbidity Index was able to identify patients at risk of major toxicities such as pleural effusion [In conclusion, the findings of this study further support bosutinib use for patients with Ph+ CP CML across age groups and mCCI scores. Age and mCCI stratification may enable the identification of patients who are at higher risk of developing TEAEs and may require more careful monitoring in clinical practice.Information about this study in a plain language format is available in the supplementary materials.