Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia

Abstract

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR.

Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

“…Changes from baseline in patient-reported outcomes measures at month 12 were comparable to those observed in previously treated patients in the initial phase 1/2 study of bosutinib, wherein long-term efficacy and HRQoL stability were reported [ 19 , 37 , 38 ]. In addition, FACT-G scores in the current study were consistent with those previously reported for bosutinib in newly diagnosed patients with CML, in the general population, as well as in patients with various cancers [ 39 – 43 ]. Maintenance of HRQoL is important for patients with CP CML who potentially will receive lifelong TKI treatment, and PRO results from this phase 4 study suggest bosutinib is a treatment option with manageable AEs, providing further support for its use in patients with CP CML resistant/intolerant to prior TKIs.…”

Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial

“…A previous analysis of BFORE demonstrated that HRQoL was maintained or improved compared with baseline after 12 months of bosutinib or imatinib treatment [ 17 ]. In addition, a pooled analysis of the bosutinib and imatinib arms showed that a better molecular response with tyrosine kinase inhibitor treatment was generally associated with improved HRQoL [ 8 ].…”

“…BFORE (ClincalTrials.gov, NCT02130557) was an open-label, randomized, multicenter, phase 3 study; methods have been published [ 7 , 8 ]. Patients aged ≥18 years, with newly diagnosed BCR::ABL1 -positive CP CML, were randomized 1:1 to receive (starting dose) bosutinib or imatinib 400 mg once daily.…”

The Effects of Tyrosine Kinase Inhibitors (TKIs) in Monotherapy and with Add-on Treatments on Health-related Quality of Life of People with Chronic Myeloid Leukemia: A Systematic Review of Randomized-Controlled Trials

“…However, while there exist substantial comparative data on the efficacy and safety of newer TKIs in the hematology field, little is known regarding HRQoL as perceived by patients with CML treated with TKIs [61]. As stated by Brümmendorf et al [43], the associations between the efficacy of treatment for CML by TKIs and HRQoL are largely unknown. In the present systematic review, out of the included seven, just two RCTs [45,47] selected HRQoL as the primary outcome, and the other two considered it as a primary outcome in association with molecular response to the TKIs therapy [40] or in a post-hoc analysis [44], after considering other clinical outcomes from the original ENEST trial [62].…”

“…The study carried out by Brümmendorf et al [43], as well as that of Cortes et al [42] just described above, regard findings from BFORE trial [41], a multicenter study primarily aimed to assess the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Brümmendorf et al [43] examined the relationships between molecular response (MR) and HRQoL after imatinib or bosutinib treatments. They represented MR values by a Log Reduction scale (MRLR), in order to consider the MRLR as a continuous variable.…”