Patient Reported Outcomes (PROs) Show Superior Quality of Life (QOL) of Patients with Chronic Myeloid Leukemia (CML) Treated with First Compared to Newer Generations of Tyrosine Kinase Inhibitors (TKIs)
Authors: Shacham Adi , Rosenman Lena , Leader Avi , Sharf Giora , Raanani Pia , Rozovski Uri 
Published: November 2019

Background: Tyrosine kinase inhibitors (TKIs) prolong the survival of patients with chronic myeloid leukemia (CML). Nowadays, the life expectancy of these patients is approaching that of an age-matched population. Since imatinib, was first introduced 20 years ago, several newer more potent TKIs, have been approved for CML. While these drugs are effective, they come with the trade-off of adverse effects, some are common to all and some are drug-specific. Most patients will receive prolonged treatment, therefore quality of life (QOL) is becoming a major concern. QOL under these drugs has not been directly compared. Herein, we compared the QOL of patients with CML treated with imatinib, dasatinib and nilotinib using patient reported outcomes (PROs) questionnaire.
Methods: This nationwide study was a joint initiative of the Israeli CML patients' organization and the division of hematology at Rabin Medical Center, Israel. Patients completed computerized questionnaires that were provided to us by the European Organization for Research and Treatment of Cancer (EORTC). The questionnaires included 30 items core questionnaire (QLQ-C30), 24 items of CML-specific questionnaire (QLQ-CML24) and additional items that were added by the researchers. Questioners are composed of functional, symptom and global health/QOL scales/items. All scales and single-item measures were standardized and the score ranges from 0 to 100. High score for functional and QOL items/scales represents better function and QOL. High score in symptoms items represents worse symptomatology. We used the Mann-Whitney test to compare medians and χ2 to compare categorical variables.
Results: Overall, 195 patients completed the questionnaire. The median age was 58 years (range: 23 to 89) and of those 102 patients (59%) were males. Time from diagnosis ranged between less than a year and 46 years (median: 7 years). In the primary analysis we included 139 patients (71%) who received either imatinib (n = 70, 36%), dastainib (n = 45, 23%) or nilotinib (n = 24, 12%). We did not include the few patients who received bosutinib (n = 8, 4%), ponatinib (n = 2, 1%) or patients who discontinued treatment (n = 22, 11%). Patients on imatinib were older (median age 67 years, range : 32 to 89) compared with patients on either nilotinib (median age 50 years, range 26 to 85 ) or dasatinib (median age 47 years, range: 26 to 85) (P<0.0001), but had similar demographics and disease characteristics. The EORTC questionnaires included 34 items related to symptoms experienced by patients within the last week. These items were grouped into 13 symptom scales. Overall, the symptomatic profile was more severe in patients who received either dasatinib or nilotinib compared with imatinib. For example, compared with patients who received dasitinib or nilotinib, patients on imatinib experienced lesser limitation on daily activities (38 and 47 vs. 25 respectively, P = 0.02), less fatigue (53 and 57 vs. 37 respectively, P = 0.001) and lesser degree of impaired body image (38 and 46 vs. 26 respectively, P = 0.022). Likewise, symptom burden score was 41 in patients on nilotinib, higher than in patients receiving dasatinib (27, P = 0.005) or imatinib (30, P = 0.018). In addition, patients on imatinib had less painful episodes compared with patients on nilotinib (28 vs. 47. P = 0.014). The questionnaire included also 18 items that were grouped into 8 scales which estimated their functional status. Compared with nilotinib, patients on imatinib had better emotional functioning (77 vs. 61, P = 0.009); patients were less worried, stressed depressed or nervous. Patients were also more satisfied of the knowledge and treatment they received by their caregivers (41 vs. 19 24, P = 0.01). Finally, although patients on imatinib were older, they reported better home and work function (67) compared with either nilotinib (50) or dasatinib (50) (P < 0.001).
Conclusions: Compared with nilotinib and dasatinib, patients who received imatinib reported lower levels of symptomatology. They reported less fatigue, limitation of daily activities, impaired body image and pain. They were also more satisfied by their caregiver, had better emotional functioning and were less worried, depressed or nervous. Since patients on 2nd generation TKIs were almost 2 decades younger, these differences reflect not only the TKI toxicity profile but also the generation-gap and the primary significance "Generation Y" gives to QOL issues.

Disclosures
Shacham: novartis: Consultancy. Sharf:Janssen: Other: Advocacy grants funding; Novartis: Honoraria, Other: Advocacy Advisory Board, Research Funding; Abbvie: Other: Advocacy grants funding; Takeda: Other: Advocacy grants funding; Incyte: Honoraria, Other: Advocacy Advisory Board, Research Funding; Pfizer: Honoraria, Other: Advocacy Advisory Board, Research Funding; BMS: Other: Advocacy grants funding, Research Funding; Roche: Other: Advocacy grants funding.