A Retrospective Cohort Study to Assess and Compare Treatment Patterns and Healthcare Utilization for Patients with Mantle Cell Lymphoma in the Veterans Affairs System (MCLOVA) Who Were Prescribed Bruton Tyrosine Kinase Inhibitors (BTKi)
Authors: Ogbeifun Henry , Kaur Supreet , Nooruddin Zohra , Nguyen Cynthia I , Gilmore Corbyn M , Vargus Adriana M , Franklin Kathleen , Jones Xavier , Frei Christopher 
Published: December 2024

Introduction: Mantle cell lymphoma (MCL) is a rare subtype (5%) of Non-Hodgkin Lymphoma (NHL), with 4-8 cases per million persons per year. Estimated 5-year survival is ~50% (~75% in patients &lt;50 years, and 36% in patients 75+ years) and has improved in the last decade. MCL incidence increases with age (median of 60-70 years) and occurs more commonly in men than women (3:1). Targeted therapies, like Bruton Tyrosine Kinase inhibitors (BTKi), BCL2 inhibitors, bispecific antibodies, and Chimeric Antigen Receptor T cell (CAR-T) therapies have improved health outcomes, but most of this evidence is derived from Phase II studies. The objective of this study was to assess and compare treatment patterns and healthcare utilization for MCL patients prescribed BTKi therapies in the Veterans Affairs (VA) system using real-world data.
Methods: This was a retrospective cohort study of adult patients (18+ years) prescribed BTKi therapies for MCL (ICD10: C83.1) in all VA medical facilities in the United States. Index date was the first date a patient with MCL was prescribed a BTKi. Patients who met study criteria in the index period (1/1/18-12/31/23) were included. Baseline characteristics were determined using data from the pre-index period (1/1/16-1/1/18). The follow-up period was from a patient's index date to their last VA visit, death, or cutoff date for this analysis (6/30/24), whichever occurred first. Duration of therapy (DOT) was last fill date, minus first fill date, +1 day, while real-world time-to-next treatment (rwTTNT) was next BTKi fill date, minus last BTKi fill date, +1 day. Healthcare visits were annualized to forecast results at 12 months. Groups were compared using chi-square and Student's t-test. P-values less than 0.05 were statistically significant.
Results: There were 3,261 MCL patients and 807 (25%) were prescribed at least one BTKi: 447 (55%) ibrutinib, 282 (35%) acalabrutinib, 177 (22%) zanubrutinib, and 41 (5%) pirtobrutinib. Too few were prescribed pirtobrutinib for further analysis. Patients had a mean ± standard deviation (SD) age of 74 ± 8 years and 99% were male. Acalabrutinib (59%, p&lt;0.01) and zanubrutinib (54%, p&lt;0.01) groups had more patients 75+ years of age than the ibrutinib (41%) group. Most patients were non-Hispanic White (86%), non-Hispanic Black (8%), Hispanic/Latinx (5%), or other non-Hispanic (1%). Charlson Age mean ± SD score was 5.74 ± 1.97 overall and was higher for patients in the acalabrutinib group than the ibrutinib group (6.05 ± 2.13 vs. 5.67 ± 1.90, p=0.01). Common Charlson comorbidities (&gt;20% prevalence) included diabetes mellitus without complications (34%), chronic obstructive pulmonary disease (25%), and renal disease (22%). Heart failure was higher for the acalabrutinib group (23%) than the ibrutinib (16%, p=0.02) or zanubrutinib (15%, p=0.02) groups. Renal disease was higher for the acalabrutinib group than the ibrutinib group (28% vs. 20%, p=0.02). Peptic ulcer disease was higher for the ibrutinib group than the acalabrutinib group (4% vs. 1%, p=0.03). Patients had an estimated 10 ± 9 lab, 37 ± 29 clinic, 0.1 ± 0.4 urgent care, 1.3 ± 2.4 emergency, and 1.0 ± 1.6 hospital visits within 12 months of being prescribed BTKi therapy. Clinic visits were higher for the ibrutinib group (43 ± 29) than the acalabrutinib (33 ± 26, p&lt;0.01) and zanubrutinib (33 ± 27, p&lt;0.01) groups. DOT for BTKi therapies (all lines) were: ibrutinib (16.3 ± 18.2 months), acalabrutinib (13.6 ± 14.0), and zanubrutinib (10.0 ± 9.9). First line BTKi use was: ibrutinib (55%), acalabrutinib (29%), zanubrutinib (16%), or pirtobrutinib (&lt;1%). First line ibrutinib was often switched to second line acalabrutinib (50%), zanubrutinib (37%), or pirtobrutinib (13%). Finally, rwTTNT for BTKi therapies (first line only) were: overall (23.1 ± 20.9 months), ibrutinib (27.4 ± 22.1), acalabrutinib (13.0 ± 12.3), and zanubrutinib (8.5 ± 6.7).
Conclusions: In this retrospective cohort study of MCL patients prescribed BTKi therapies in the VA, there were significant differences in patient characteristics, comorbidities, and healthcare utilization. This might represent clinician preference for prescribing certain BTKi therapies in special populations and might impact effectiveness of those therapies. Time since market entry might partially account for the DOT and rwTTNT results. More evidence is needed to determine if personalized BTKi prescribing can improve health outcomes or decrease adverse events.