Zanubrutinib Associated With Longer Treatment Persistence, Duration, and TTD in Real-World MCL

A real-world, retrospective, observational analysis evaluating United States patients with mantle cell lymphoma (MCL) treated with ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa) showed that those treated with zanubrutinib experienced longer treatment persistence, treatment duration, time to discontinuation (TTD), and lower switching rates compared with acalabrutinib and ibrutinib.¹

Data presented in a poster at the28th International Congress on Hematologic Malignancies demonstrated that persistence rates significantly varied across the 3 BTK inhibitors among patients who received treatment with ibrutinib (n = 693), acalabrutinib (n = 697), or zanubrutinib (n = 284) for at least 360 days (P = .0079), and zanubrutinib exhibited the highest persistence rates. At 90 days, the persistence rate was 66.9% for zanubrutinib, 56.3% for ibrutinib, and 62.7% for acalabrutinib. After 360 days, zanubrutinib maintained the highest persistence rate at 16.9% compared with 10.8% for ibrutinib and 13.2% for acalabrutinib.

Although ibrutinib, acalabrutinib, and zanubrutinib have been approved by the FDA for the treatment of patients with relapsed/refractory MCL, uncertainty remains regarding the real-world utilization and treatment patterns with these BTK inhibitors in this patient population. Notably, in April 2023, AbbVie announced the intention to voluntarily withdraw the indication for ibrutinib in patients with MCL who have previously received at least 1 therapy.²

The retrospective, observational study utilized the Symphony Integrated Dataverse—an extensive, longitudinal database comprising open claims and integrated electronic medical records. The study included patients at least 18 years of age with MCL who began treatment with a BTK inhibitor between January 1, 2020, and December 31, 2022.¹

Inclusion criteria called for continuous enrollment for at least 365 days leading up to the initiation date of BTK inhibitor therapy and a minimum of 90 days following the initiation date. Three cohorts of patients were established based on initiation of treatment with ibrutinib, acalabrutinib, or zanubrutinib. Patients were tracked until the conclusion of the study on March 31, 2023, or until they were lost to follow-up.

Treatment persistence was evaluated by the proportion of patients prescribed a BTK inhibitor for 80% or more of the days covered across 30-day intervals. Health care resource utilization was determined by outpatient visits and inpatient services per patient per month during treatment. Additionally, TTD was defined as the time from BTK inhibitor initiation to cessation with a gap of at least 60 days between the prescription of a subsequent BTK inhibitor. Treatment duration was defined as the time from BTK inhibitor initiation to the end date of the last prescription.

The goal of this study was to examine treatment patterns, persistence, and health care resource utilization in the ibrutinib, acalabrutinib, and zanubrutinib cohorts.

Across the 3 cohorts, the majority of patients were male (acalabrutinib, 69%; ibrutinib, 73.9%; zanubrutinib, 69.5%); the median age was 73 years (interquartile range [IQR], 65-77), 71 years (IQR, 64-77), and 72 years (IQR, 65-78), respectively, and most patients were over 65 years of age (76.6%; 74.5%; 77.3%); payer types included Medicare (61.8%; 55.8%; 55.3%), commercial (31.9%; 36.0%; 39.7%), and other (6.3%; 8.3%; 5.0%). Additionally, patients received prior first-line treatment (72.7%; 61.7%; 71.3%), prior second-line treatment (11.8%; 11.8%; 14.2%), or no prior treatment (15.4%; 26.5%; 14.5%). The median Charlson Comorbidity Index was 6 across all groups.

Furthermore, the median follow-up duration was 392 days for acalabrutinib, 471 days for ibrutinib, and 340 days for zanubrutinib. Baseline clinical characteristics were well-balanced across the cohorts, except for a notable difference in the mean number of prior lines of therapies, which was highest for zanubrutinib (1.01 [standard deviation (SD), 0.58) compared with acalabrutinib (0.98 [SD, 0.56]) and ibrutinib (0.86 [SD, 0.64]).

Additional data showed that 23.8% of patients initially treated with ibrutinib switched to acalabrutinib (72.7%) or zanubrutinib (27.3%); 5.6% of patients initially given acalabrutinib switch to ibrutinib (41.0%) or zanubrutinib (59.0%); and 2.8% of patients initially treated with zanubrutinib switched to ibrutinib (50%) or acalabrutinib (50%).

Patients in the zanubrutinib group experienced a median TTD of 188.5 days compared with 161.5 days for ibrutinib and 179 days for acalabrutinib. Additionally, the median treatment duration was 200 days for zanubrutinib vs 171 days for ibrutinib and 194 days for acalabrutinib.

Regarding health care resource utilization, the mean outpatient visits were 1.53 (SD, 2.5) for zanubrutinib, 1.59 (SD, 2.96) for ibrutinib, and 1.95 (SD, 3.49) for acalabrutinib. The mean inpatient services were 0.56 (SD, 2.21), 0.71 (SD, 3.84), and 0.83 (SD, 4.02), respectively, and the mean number of other medical or hospital services was 1.17 (SD, 2.4), 1.1 (SD, 2.39), and 1.12 (SD, 2.44), respectively.

Regarding baseline comorbidities, general fatigue levels were elevated in the zanubrutinib group (12.1%) compared with both the acalabrutinib group (7.2%) and ibrutinib group (6.5%). However, no significant differences were observed across the cohorts for other measured comorbidities.

References

1. Yang K, Shah B, Xue M, et al. Real-world switching pattern, persistence, and associated healthcare resource utilization of bruton tyrosine kinase inhibitors for the treatment of mantle cell lymphoma in the United States. Presented at: 28th International Congress on Hematologic Malignancies; February 29 to March 3, 2024. Miami, FL.
2. Update on Imbruvica (ibrutinib) US accelerated approvals for mantle cell lymphoma and marginal zone lymphoma indications. News release. AbbVie. April 6, 2023. Accessed April 17, 2024. https://news.abbvie.com/2023-04-06-Update-on-IMBRUVICA-R-ibrutinib-U-S-Accelerated-Approvals-for-Mantle-Cell-Lymphoma-and-Marginal-Zone-Lymphoma-Indications