Real-World Testing and Treatment Patterns in Chronic Lymphocytic Leukemia (CLL) in the United States during the Modern Era: A SEER Patterns of Care Analysis

Introduction: The use of fluorescence in situ hybridization (FISH) and IgVH mutation analyses were initially used to help prognosticate CLL patients in clinical trials. In the modern era of Bruton tyrosine kinase inhibitors and improved response rates in patients with deletion 17p, and demonstrated long-term remissions among mutated IgVH patients treated with fludarabine, cyclophosphamide and rituximab (FCR), the use of testing prior to treatment is now considered standard of care to determine appropriate therapy. Several therapies were FDA approved for CLL since 2008 through 2014, including bendamustine and novel therapeutics (obinutuzumab, ibrutinib, and idelalisib). We aimed to look at patterns of real-world testing frequencies and treatment patterns by comparing two United States population based samples of untreated and treated CLL patients in 2008 and 2014.

Methods: The National Cancer Institute sponsored Patterns of Care (POC) study was conducted in a population of CLL patients, randomly sampled from 13 Surveillance, Epidemiology, and End Results (SEER) program registries, diagnosed in 2008 and again in 2014. Trained abstractors collected data on demographics, diagnostics, testing, and treatments from patient medical records within 24 months post-diagnosis (along with a physician verification survey). Patient characteristics were described by age, sex, race, Charlson comorbidity index, area-based socioeconomic status, insurance status, receipt of systemic therapy, and type of treatments by diagnosis year. Patient characteristics and frequency of testing (FISH and IgVH mutation analyses) in 2008 and 2014 were compared using Rao-Scott chi-square tests. Logistic regression taking into account sampling weights was used to estimate odd ratios and 95% confidence intervals for receipt of FISH testing, both unadjusted and adjusted for age, sex, race, insurance status, and receipt of systemic treatment. Adjusted models were run overall and stratified by age at diagnosis (<65 and ≥65).

Results: This study included 1,008 CLL patients diagnosed in 2008 and 1,367 CLL patients diagnosed in 2014. The mean age was 69.6 years in 2008, and 68.0 years in 2014. Among those with a known status for FISH testing, the proportion of patients who underwent testing was 51.3% in 2008, which increased to 59.6% in 2014 (p<0.01). Among those with a known status for IgVH mutation analyses, 8.5% underwent testing in 2008, which increased to 15.1% in 2014 (p<0.01). Older age was a strong predictor for not receiving FISH testing in both 2008 and 2014 (adjusted p-trend <0.01 for both years). In 2014, Hispanic patients were less likely to undergo testing (aOR 0.68, 95% CI: 0.48-0.96) compared to non-Hispanic whites, but no significant difference was found among non-Hispanic blacks. Among patients 65 or older, those with Medicare without private insurance were less likely to receive testing compared to Medicare patients with private insurance (aOR 0.49, CI: 0.32-0.74).

Most CLL patients were untreated within the first two years from diagnosis (74.3% in 2008, and 70.6% in 2014). FISH testing occurred in a majority but not all patients who received therapy (64.5% of treated patients in 2008, increased to 74.7% in 2014). In 2008, the four most frequently used regimens for first treatment were 1) FCR, 2) rituximab monotherapy, 3) FR, and 4) chlorambucil based regimens. This is in contrast to 2014, where the regimens were 1) bendamustine and rituximab (BR), 2) rituximab monotherapy, 3) FCR, and 4) ibrutinib. When evaluating the use of novel therapies (obinutuzumab, ibrutinib, and idelalisib) for those diagnosed in 2014, there were no significant differences in distribution by age, race/ethnicity, comorbid conditions, SES, or insurance type.

Conclusions: There has been an increase in frequency of FISH testing and IgVH mutation analyses from 2008 to 2014. FISH testing is more common compared to IgVH mutation analyses which was modest in both years. Patients of older age, Hispanic ethnicity, and Medicare with no private insurance were also less likely to receive FISH testing in 2014. There are significant differences in the treatment patterns of patients in 2008 compared to 2014, with the use of bendamustine being more common at the expense of FCR. These results highlight rapidly changing practices within CLL in the modern era.