Real-World Analysis of the Clinical and Economic Burden of Later Line in Chronic Myeloid Leukemia Patients in Italy
Authors: Breccia Massimo , Chiodi Francesca , Valsecchi Diletta , Perrone Valentina , Sangiorgi Diego , Giacomini Elisa , Rendace Maria Chiara , Coco Paola , Premoli Eleonora , Degli Esposti Luca 
Published: November 2021

Abstract
Background
The use of real-world data in oncology is gaining increasing interest, as it can provide valuable insights into treatments and related outcomes in routine daily oncology practice, thus integrating the evidence coming from clinical trials. The study aims to describe the characteristics of patients (pts) with chronic myeloid leukemia (CML) in 2 nd or ≥3 rd tyrosine kinase inhibitors (TKI) lines of therapy, analyze their drug utilization and evaluate healthcare direct costs for the Italian National Health Service in order to estimate the impact of disease burden.
Methods
This retrospective observational analysis was based on administrative databases covering around 15.3 million subjects in Italy. All adult pts with prescription of the TKIs bosutinib (BOS), dasatinib (DAS), imatinib (IMA), nilotinib (NIL), ponatinib (PON) in 2 nd or ≥3 rd line of therapy during 01/2015-12/2018 were included. Specifically, those with IMA, DAS or PON prescription were enrolled if they also presented ≥1 CML hospitalization or previous prescription for NIL or BOS or ≥1 BCR-ABL1 RQ-PCR test without hospitalization for acute lymphoid leukemia. Pts enrolled in clinical trials were not captured. Index date was 1 st prescription date for a TKI in 2 nd or ≥3 rd line. Comorbidities were assessed by hospitalization diagnosis codes and/or presence of specific drugs as proxy of diagnosis. Mean annual healthcare resource costs were evaluated during follow-up (from index date to end of study) in terms of drugs other than TKI (excluded), visits, tests, hospitalizations (overall and comorbidity-related during treatment).
Results
Overall, 491 pts in 2 nd and 144 in ≥3 rd line were included. In each calendar year from 2015 to 2018, the incidence of pts who entered a 2 nd line changed from 22.6% to 28.7%, whereas the ≥3 rd line fluctuated from 37% to 46.7%. An increment of 97.6% was observed in the number of pts treated in ≥3 rd line from 2015 to 2018 (figure 1). As 2 nd line, 40.9% was represented by DAS, 28.9% NIL, 12.2% BOS, 10.2% PON and 7.8% IMA. Mean age ranged from 56.1 (PON) to 68.2 (BOS) years. At baseline, hypertension was the most reported comorbidity (from 64.1% for NIL to 91.7% for BOS), followed by metabolic (from 27.9% in DAS pts to 63.2% for IMA) and blood count (from 28.4% for DAS to 58.0% for PON) alterations. Among pts in ≥3 rd line, 26.3% received imatinib, 22.2% PON, 18.8% NIL, 16.7% BOS, 16% DAS. Mean age was 57 years for NIL, 64.8 PON and 69.5 BOS pts. Same trend of comorbidities was reported in the ≥3 rd line cohort, with hypertension detected in all pts starting BOS to a minimum of 65.2% pts in DAS group, followed by blood count alteration (34.8% for DAS to 59.4% for PON) and metabolic alterations (37.0% for NIL to 50.0% for BOS). Baseline cardiovascular comorbidities were present in 22.8% of pts starting a 2 nd line and in 35.4% of pts starting ≥3 rd line. After a median follow up of 3.0 and 2.6 years, 13% and 19% of pts died in 2 nd and ≥3 rd lines, respectively, around 40% in both lines discontinued their treatment. Median time to discontinuation was 5.5 (95%CI: 4.7-6.2) (2 nd line) and 4.3 (95%CI: 3.2-5.2) (≥3 rd line) years. Mean number of annual hospitalizations was 0.6 (from 0.4 for NIL to 1.1 for PON) in 2 nd line, and 0.5 (from 0.4 for IMA and NIL to 0.7 for PON) in ≥3 rd line. Total mean annual costs/pts (TKI excluded) were of €10,168 (PON), €6,106 (BOS), €5,086 (DAS), €4,779 (NIL) and €3,905 (IMA), with hospitalizations comorbidity-related accounting for €3,245 among PON, €2,820 BOS, €1,739 NIL, €1,573 DAS and €1,448 IMA pts. Mean annual costs per lines are shown in figure 2.
Conclusions
This real-world study provided a demographic and clinical profile of CML pts in 2 nd and ≥3 rd TKI lines and described drug utilization and resource consumption in the Italian clinical practice setting. An increase of pts treated with TKIs in ≥3 rd line was reported, reflecting the availability of multiple TKIs over the years; moreover, a highly comorbid population suggests an increasingly complex CML management. Our results underlined a heavy clinical and economic burden for pts in 2 nd or ≥3 rd lines, especially in terms of comorbidities, treatment discontinuation and hospitalizations suggesting the need of novel therapeutic options for management of later lines CML.
Figure 1 Figure 1.

Disclosures
Breccia: Novartis: Consultancy; Pfizer: Consultancy; BMS: Consultancy; INCYTE: Consultancy; Abbvie: Consultancy. Chiodi: Novartis: Current Employment. Valsecchi: Novartis Farma SpA: Current Employment. Rendace: Novartis Farma S.p.A.: Current Employment. Coco: Novartis Farma S.p.A.: Current Employment. Premoli: Novartis Farma SpA: Current Employment.