Studies on Survival, Effectiveness, and Cost Outcomes of First Line Treatments in Chronic Lymphocytic Leukemia

Abstract

With the approval of targeted therapies as first line treatments in patients with chronic lymphocytic leukemia (CLL), the National Comprehensive Cancer Network (NCCN) guidelines list these agents as monotherapy or combined with immunotherapy as the preferred front-line regimens regardless of age, comorbidity, and 17p deletion/TP53 mutation or IGHV mutation status. Therefore, more challenges in choosing between treatments has been in the clinical practices especially by the absence of direct evidence or real-world data that compare between all treatments. We sought in this research to establish evidence that compares between all treatments in regards of effectiveness, survival, and costs. In an analysis of evaluating survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) database (1985-2017), the relative survival rates, cure proportions and hazard of death rates were significantly improved for patients who followed to the era of advanced therapies. A second analysis of network meta-analysis on all survival curves of the published trials revealed that acalabrutinib-plus-obinutuzumab showed significant differences in the progression free survival (PFS) outcomes when compared with ibrutinib. While ibrutinib was not statistically significant from the other targeted therapies. Among patients with low-risk disease, there was no difference between the PFS of targeted therapies and chemoimmunotherapies, but probable gain in the time-to-next-treatment (TTNT) after administering targeted therapies can be achieved. In last analysis that compared the relative effectiveness with treatment’s costs found that patients who are treated with targeted therapy “venetoclax-plus-obinutuzumab” gain more health benefits and less cost when compared with all chemoimmunotherapies, while the other targeted therapies achieve higher benefits than venetoclax-plus-obinutuzumab but with higher costs. Overall, there are always superiority of targeted agents over chemoimmunotherapies in treating CLL patients, who are older than 65 years or having comorbidities, especially in patients with high-risk disease as having unmutated IGHV or del 17p. Acalabrutinib-plus-obinutuzumab is the combination that achieved the highest effectiveness outcomes in term of PFS and TTNT but with higher costs than others.