Patients with mantle cell lymphoma (MCL) treated with zanubrutinib (Brukinsa) in the community oncology setting achieved longer treatment durations, higher treatment adherence rates, and lower rates of treatment discontinuation compared with patients who received other BTK inhibitors, according to a real-world, retrospective, observational study of treatment patterns with BTK inhibitors, which was published in Future Oncology.1
In total, 402 patients began treatment with ibrutinib (Imbruvica; n = 197; average follow-up, 746 days), acalabrutinib (Calquence; n = 161; average follow-up, 701 days) or zanubrutinib (n = 44; average follow-up, 493 days). Patients who received zanubrutinib had a significantly longer median duration of treatment, at 292 days, compared with those who received acalabrutinib (259 days) or ibrutinib (149 days; P < .01). Patients treated with zanubrutinib also displayed significantly better treatment adherence at more than 60, more than 90, more than 180, and more than 360 days compared with those who received acalabrutinib or zanubrutinib (P < .05). The rates of treatment adherence for more than 360 days in these respective cohorts were 53%, 45%, and 31%.
Real-World Outcomes With BTK inhibitors in MCL: Key Takeaways
- A real-world retrospective analysis found that patients with MCL treated with zanubrutinib had significantly longer median duration of treatment, higher treatment adherence, and the lowest rate of treatment discontinuation compared with those who received acalabrutinib or ibrutinib.
- Although the study showed no significant differences in the incidence of clinical events between the cohorts during the 180-day follow-up period, patients in the zanubrutinib cohort had numerically lower rates of specific events like atrial fibrillation and fever compared with patients in the acalabrutinib and ibrutinib cohorts.
- The results indicated strong outcomes for zanubrutinib in the post-BTK inhibitor setting, considering that 50% of the patients in the zanubrutinib group had a history of prior BTK inhibitor exposure before starting zanubrutinib treatment.
Patients in the zanubrutinib cohort also had the lowest treatment discontinuation rate during follow-up, at 43.2% vs 45.2% in the ibrutinib cohort and 51.6% in the acalabrutinib cohort. The rates of treatment discontinuation due to toxicity in these respective cohorts were 13.6%, 13.2%, and 17.4%. The respective rates of treatment discontinuation due to nonresponse, disease progression, or worsened comorbidities were 18.2%, 24.9%, and 23.0%.
“Overall, there were no significant differences between the BTK inhibitor cohorts in clinical events over the 180-day follow-up period,” lead study author Bijal Shah, MD, MS, and coauthors wrote in the paper. “However, the acalabrutinib and zanubrutinib cohorts generally had numerically lower rates of clinical events than the ibrutinib cohort. As the data mature, there could be an increase in time to next treatment and treatment duration for patients with MCL receiving zanubrutinib- or acalabrutinib-based treatment regimens.”
Shah is an associate member in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida.
What Are the Current Indications for BTK Inhibitors in MCL?
In 2013, the FDA granted accelerated approval to ibrutinib for patients with MCL who had received at least 1 prior therapy.2 However, in 2023, this indication was voluntarily withdrawn by Johnson & Johnson and AbbVie citing insufficient data from the phase 3 SHINE confirmatory trial to support conversion to full approval.3 Furthermore,
Furthermore, acalabrutinib is indicated in combination with bendamustine plus rituximab (Rituxan) for the treatment of adult patients with treatment-naive MCL who are ineligible for autologous stem cell transplant, as well as the treatment of adult patients with MCL who have received 1 or more prior lines of therapy.4 Additionally, zanubrutinib is approved for the treatment of adult patients who have received at least 1 prior therapy.5
What Was the Design of the Real-World Retrospective Analysis of BTK Inhibitors in MCL?
This retrospective analysis included electronic medical records from patients with MCL across 17 community oncology networks in the United States who began treatment with a BTK inhibitor between January 1, 2019, and November 30, 2021.1 Patients were followed for at least 6 months and examined for baseline characteristics and treatment outcomes.
To be included in the study, patients were required to initiate a new BTK inhibitor–based regimen during the retrospective study index period and have at least 1 MCL diagnosis on the date of their first BTK inhibitor claim or during the pre-index period. Patients were excluded from the study if they were younger than 18 years of age at index, did not have a valid prescription or medical claim in the 3 months prior to the study index date, or did not have a valid prescription or medical claim in the 6 months following the study index date.
Patients were stratified by the type of BTK inhibitor they initiated during the index period (acalabrutinib vs zanubrutinib vs ibrutinib). If patients began treatment with more than 1 BTK inhibitor–based regimen during this period, they were stratified based on a hierarchical approach.
What Were the Baseline Characteristics of Patients Included in the Retrospective Analysis of BTK Inhibitors in MCL?
Among all patients included in the study, 93% had received 1 or more systemic lines of therapy for MCL. In total, 50% of patients in the zanubrutinib group had a history of BTK inhibitor exposure prior to zanubrutinib; of these patients, 63.6% had received the previous BTK inhibitor within 60 days of initiating zanubrutinib.
“The results of this analysis also show strong outcomes for zanubrutinib in the post-BTK inhibitor setting.”
Additionally, 29.2% of patients in the acalabrutinib group had previously received another BTK inhibitor before acalabrutinib; 57.4% of these patients had received the prior BTK inhibitor within 60 days of initiating acalabrutinib. The study design required that no patients in the ibrutinib arm have a history of BTK inhibition prior to ibrutinib.
At the start of study-specified BTK inhibitor therapy, the median ages of patients were similar between the zanubrutinib (75 years; range, 56-89), acalabrutinib (76 years; range, 36-89), and ibrutinib (72 years; range, 36-89) cohorts (P < .01). Furthermore, the percentages of patients who were at least 65 years of age were similar among the cohorts. Overall, investigators reported no significant differences across the cohorts regarding race, gender, ethnicity, or payer type.
Regarding comorbidities, the incidence of chronic pulmonary disease during the pre-index period was significantly different between the zanubrutinib, acalabrutinib, and ibrutinib cohorts, at 25.0%, 16.8%, and 12.7%, respectively (P = .04). However, there were no significant differences among the cohorts regarding the prevalence of other prespecified comorbidities during the pre-index period, although patients in the zanubrutinib cohort had numerically highest rates of atrial fibrillation, cardiac arrhythmias, diabetes, gastroesophageal reflux disease, and renal disease. Conversely, patients in the acalabrutinib cohort had numerically the highest rates of cardiovascular disease and hypertension.
What Additional Findings Were Seen in the Analysis of Real-World BTK Inhibitor Outcomes in MCL?
During the 180-day follow-up period, no significant differences in the rates of clinical events between the cohorts were reported. Patients in the zanubrutinib cohort had the lowest rate of atrial fibrillation, at 9.1%, and no cases of atrial flutter were observed in this cohort. Additionally, the incidence of fever was lowest in the zanubrutinib arm, at 4.5% vs 12.4% in the acalabrutinib cohort and 16.8% in the ibrutinib cohort. Furthermore, the rates of myocardial infarction in these respective cohorts were 4.5%, 4.3%, and 7.6%.
“Further analyses using more recent data and a longer time horizon are needed to validate these outcomes,” the authors concluded.
References
- Shah BD, Xue M, Furnback W, Yang K. Real-world treatment patterns of Bruton tyrosine kinase inhibitors in mantle cell lymphoma in a community oncology setting. Future Oncol. 2025;21(23):3043-3049. doi:10.1080/14796694.2025.2554354
- Imbruvica (ibrutinib) capsules now approved in the US for mantle cell lymphoma patients who have received at least one prior therapy. News release. Janssen Biotech, Inc. November 13, 2013. Accessed October 10, 2025. https://www.jnj.com/media-center/press-releases/imbruvica-ibrutinib-capsules-now-approved-in-the-us-for-mantle-cell-lymphoma-patients-who-have-received-at-least-one-prior-therapy
- Update on Imbruvica (ibrutinib) US accelerated approvals for mantle cell lymphoma and marginal zone lymphoma indications. News release. AbbVie. April 6, 2023. Accessed October 10, 2025. https://www.jnj.com/media-center/press-releases/update-on-imbruvica-ibrutinib-u-s-accelerated-approvals-for-mantle-cell-lymphoma-and-marginal-zone-lymphoma-indications
- Calquence. Prescribing information. AstraZeneca; revised January 2025. Accessed October 10, 2025. https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/e2a005a7-65a0-4388-a671-dc887815a938/e2a005a7-65a0-4388-a671-dc887815a938_viewable_rendition__v.pdf
- Brukinsa. Prescribing information. BeOne; revised June 2025. Accessed October 10, 2025. https://d1e94vsyskgtht.cloudfront.net/brukinsa/pdfs/brukinsa-prescribing-information.pdf
