Inpatient systemic therapy for CLL/SLL in the United States, 2016–2022: Trends, disparities, and the shift from chemotherapy to monoclonal antibodies

Abstract Background: Though CLL/SLL care has shifted to outpatient targeted and immune therapies, contemporary national patterns of inpatient systemic treatment, their temporal evolution with adoption of targeted agents, and variation by patient, payer, and hospital characteristics remain poorly defined. We therefore quantified 2016 - 2022 trends in inpatient systemic therapy modalities and examined differences across demographic, payer, and site-of-care strata. Methods: We conducted a retrospective analysis of the HCUP National Inpatient Sample (NIS, 2016 - 2022), a ~20% stratified, self-weighted sample of U.S. community hospital discharges, identifying adult CLL/SLL hospitalizations via ICD-10 codes. Inpatient therapies were classified as: (1) chemotherapy; (2) monoclonal antibody (MAb); (3) chemo + MAb; (4) bone marrow/stem cell transplant (BMT/SCT); (5) CAR-T; and (6) leukapheresis. Annual modality-specific rates (%) were calculated against total CLL/SLL discharges. Overall and stratified time-trends by age (< 50, 50 - 59, 60 - 69, 70 - 79, ≥ 80 years), race/ethnicity (White, Black, Hispanic, Asian/PI, Native American, Other, Missing), payer, urbanicity, teaching status, and U.S. census region were evaluated using the Cochran-Armitage test for trend (two-sided α = 0.05). The 95% confidence interval for the 2016-2022 difference reflects a pairwise endpoint comparison. Results: Utilization over time. Among N = 117,765 CLL/SLL inpatient admissions from 2016 - 2022, inpatient systemic therapy occurred in 3,523 admissions (2.99%). Overall, inpatient treatment decreased from 2.89% to 2.67% (Cochran-Armitage p = 0.013). Chemotherapy fell from 2.61% (2016) to 1.76% (2022) with an absolute change −0.85 percentage points (pp) (95% CI −1.17 to −0.54); RR 0.67 (95% CI 0.58 - 0.78). Monoclonal antibody use more than doubled from 0.40% to 1.03%; +0.63 pp (95% CI 0.45 - 0.80); RR 2.58 (95% CI 1.94 - 3.43); both p < 0.001. Leukapheresis increased modestly (p = 0.01) from 0.01 - 0.06%. BMT/SCT remained single digit (n = 1-6) each year and did not show a trend. Chemo+mAb was stable (p = 0.26). CAR-T first appeared in 2022 (0.05%; n = 9). Patient factors. All subgroup comparisons are unadjusted. Treatment was more common in men than women (3.22% vs 2.26%, overall p < 0.001); absolute difference +0.96 pp (95% CI 0.78 - 1.14); RR 1.42 (95% CI 1.33 - 1.53), with a small decrease over time in men (p = 0.007) and no trend in women (p = 0.46). Rates declined with age (< 50 y 10.2%, 50 - 59 y 7.39%, 60 - 69 y 5.18%, 70 - 79 y 2.85%, ≥ 80 y 0.88%; all-years p < 0.001); < 50 y vs ≥ 80 y: RD +9.32 pp (95% CI 8.01 - 10.63), RR 11.6 (95% CI 9.86 - 13.62). Payer & hospital factors. By primary payer, utilization was highest for Private/HMO 6.82% (decreasing over time, p = 0.016) versus Medicaid 4.95% and Medicare 2.25% without trend (inter-group p < 0.001). Effect sizes: Private vs Medicare RD +4.57 pp (95% CI 4.15 - 4.99), RR 3.03 (95% CI 2.82 - 3.26); Medicaid vs Medicare RD +2.70 pp (95% CI 2.07 - 3.33), RR 2.20 (95% CI 1.93 - 2.51). Utilization was higher in urban (3.79%) vs rural (0.94%) hospitals - RD +2.85 pp (95% CI 2.68 - 3.02), RR 4.03 (95% CI 3.59 - 4.53) - and higher in non-teaching (3.42%) vs teaching (1.18%) facilities - RD +2.24 pp (95% CI 2.06 - 2.42), RR 2.90 (95% CI 2.56 - 3.28); both decreased over time (p ≤ 0.003). Regionally, Northeast 3.79% (down-trending p = 0.04) vs Midwest 2.58%, South 2.85%, West 2.91% without trend (inter-group p < 0.001). These patterns highlight equity/operations gradients across payer and site-of-care categories. Conclusions: In contemporary U.S. inpatient practice for CLL/SLL (2016-2022), systemic therapy is uncommon (~ 3%) and decreasing, with a clear shift away from chemotherapy toward monoclonal antibodies and nascent inpatient CAR-T use in 2022. Utilization shows consistent, unadjusted gradients - higher in younger patients, men, privately insured individuals, urban and non-teaching hospitals - indicating operational/access differences rather than biology. For clinical practice, these data support defaulting to outpatient-directed pathways, reserving inpatient therapy for urgent indications, with targeted equity efforts for rural/teaching settings and Medicare/Medicaid populations. Although inpatient-only, the trends are robust and immediately actionable for service planning and quality improvement, while future linkage to outcomes and outpatient data can refine value and effectiveness assessments.