Background: In patients with CLL/SLL, high risk genetic abnormalities are associated with inferior responses to CIT, and the economic burden of this remains uncertain. This study aimed to compare real world clinical and economic outcomes in high risk and perceived non-high risk patients initiating 1L CIT. Methods: This retrospective cohort study identified patients with CLL/SLL from the HealthCore Integrated Research Database representing a national managed care population with over 58 million members. Medical records were obtained for eligible patients who initiated 1L CIT between 1/1/2007 and 7/31/2019 and underwent prognostic testing to classify them as high risk (HR: del17p, TP53 mutation, del11q or unmutated IGHV) or as non-high risk by FISH only (NHR: non-del17p and non-del11q). The first CIT claim date was the index date. Patients were required to have ≥12 months of pre-index and ≥30 days of post-index eligibility. Study outcomes included testing rate, time to next treatment (NT) or death, time to treatment failure (TF; defined as time to change of therapy, non-chemotherapy intervention, hospice care or death), and total plan paid costs (medical + pharmacy) per patient per month (PPPM) in the 1L period. Cox proportional hazard models and generalized linear models were used to calculate adjusted hazard ratio or rate ratio. Results: Among the 1,808 patients with CLL/SLL, 612 were FISH or IGHV tested and the rate of testing increased from 2007 to 2019 (30% to 44%), especially after adding ibrutinib for 1L CLL with del17p in NCCN guidelines v4.2014. Risk status was available for 253 patients (HR: 119; NHR: 134), with 80% of patients initiating 1L BR/FCR-based therapy in both cohorts. Median follow up was 26.4 vs. 25.8 months (HR vs NHR). HR patients had 65% higher risk of NT/death (median time: 2.4 vs 3.7 years), and 65% higher risk of TF (median time: 3.0 vs 4.9 years) compared to NHR patients (Table). The total costs PPPM were also significantly higher for HR patients in the 1L period ($12,194 vs $9,055, p=0.027; Rate Ratio=1.33, p<0.001). Conclusions: Initiating 1L CIT among HR patients with CLL/SLL was associated with increased risks of NT/death, TF, and higher costs compared to NHR patients identified by FISH only. Assessment of cytogenetic/molecular risk status for appropriate treatment is vital to optimize clinical and economic outcomes, especially in the novel agent era. Recent testing practices to assess genetic risk in CLL remains suboptimal.

¹Adjusting for age, gender, plan type, baseline clinical conditions and costs.