Real-world chronic lymphocytic leukemia (CLL)–specific biomarker testing patterns and frontline treatment patterns in patients with CLL/small lymphocytic lymphoma (SLL)

Abstract Introduction: CLL/SLL is the most common leukemia in adults in the United States, with ~21,000 cases diagnosed annually. National Comprehensive Cancer Network (NCCN) guidelines recommend testing for certain prognostic variables prior to initiation of CLL/SLL treatment (tx). For patients (pts) with higher-risk genomic aberrations (eg, del17p, TP53 gene mutation, unmutated immunoglobulin heavy chain variable region IGHV) targeted agents such as second-generation Bruton tyrosine kinase (BTK) inhibitors are preferred over chemoimmunotherapy (CIT) or ibrutinib as frontline (1L) tx options (NCCN, 2024; CLL Society, 2024). However, genomic testing patterns may differ by geographic region or institution. Baylor Scott 22.9% vs 17.6%), and more likely to have commercial insurance (26.4% vs 20.3%). In addition, pts without FISH testing were more likely to have missing SVI (18.2% vs 8.6%). Among those with SVI, pts without FISH testing were more likely to live in areas with median-high or high SVI (49.1% vs 42.2%). Among pts with test orders, most had orders prior to 1L therapy orders (FISH, 85.0%; TP53, 90.9%; IGHV, 84.6%). Pts with FISH testing were more likely than those without FISH testing to receive a regimen of BTK inhibitor monotherapy (60.7% vs 48.7%, respectively) or B-cell lymphoma 2 (BCL2) inhibitor + anti-CD20 therapy (13.6% vs 5.3%) and were less likely to receive a regimen of CIT (9.3% vs 14.4%). Additionally, pts with FISH testing were more likely to receive second-generation BTK inhibitors versus those without FISH testing (44.3% vs 34.2%, respectively). In a multivariable analysis, pts with unknown SVI had 63.6% lower odds of receiving FISH testing than those with known SVI (odds ratio OR: 0.36; 95% CI, 0.15-0.86). Missing SVI is likely a proxy for an unreliable residential address. In contrast, pts with a test order for β-2 microglobulin were more likely to receive FISH tests (OR, 2.34; 95% CI, 1.39-3.94).Conclusions: In this real-world study among pts treated in an integrated delivery system in Texas, frequencies of test orders for CLL-specific biomarkers, especially DNA sequencing for TP53 and IGHV, remained low in recent years. Pts with testing were more likely to receive second-generation BTK inhibitor- or BCL2 inhibitor-based tx, while pts without testing were more likely to receive CIT. The observed differences in testing rates by tx groups and factors associated with social and practice patterns highlight opportunities to improve quality of care and optimize tx decisions.