Real-World Effectiveness and Safety Outcomes of Acalabrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma

Introduction: Acalabrutinib (acala) is an approved oral Bruton tyrosine kinase inhibitor (BTKi) for the treatment of adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) following at least 1 prior therapy. Current evidence demonstrating benefits with the use of acala in MCL in real-world (RW) practice is limited. In a previously presented RW analysis using an electronic health records (EHR) database of US patients (pts) with MCL receiving second-line or third-line acala monotherapy, at a median follow-up of 35 months (mo), the median RW time to next treatment was 11.5 mo and median RW overall survival was 27.4 mo (Phillips et al. EHA 2024. Abstract #P1139). This observational study used a claims database to further describe RW effectiveness and safety outcomes in US pts with MCL receiving acala as monotherapy or in a combination regimen who were not part of a clinical trial.

Methods: This retrospective analysis used claims data from the US-based Optum Clinformatics® Data Mart to identify pts age ≥18 years diagnosed with MCL who initiated acala as a single agent or as part of a combination regimen on or after Oct 31, 2017 (FDA approval for acala). Pts with MCL were included if they had ≥6 mo of continuous enrollment in the Optum database prior to acala initiation. For this analysis, only pts receiving acala in the R/R setting are described. Pts were followed to the earliest of last data availability, death, or end of study period (Sept 30, 2022). Treatment effectiveness was described as time to next treatment (TTNT, defined as time from acala initiation to date of next treatment initiation or death) and OS (defined as time from index date to date of death). Pts were censored at the date of their last known activity, end of follow-up, or disenrollment. Cardiovascular (CV) events, infection, and other toxicity events were analyzed descriptively in all pts following acala initiation. A Kaplan-Meier analysis was used to estimate TTNT and OS.

Results: Among 181 pts with MCL treated with acala, 127 were treated in the R/R setting (study cohort) (acala monotherapy: 94 pts; combination therapy: 33 pts). Pts were mostly male (70.9%), had a median age of 75 y (50.4% were ≥75 y), and had a high comorbidity burden (mean Charlson comorbidity index score of 3.68). The most common CV risk factors at baseline were hypertension (79.5%), diabetes (64.6%), peripheral arterial disease (50.4%), hypercholesterolemia (38.6%), cerebrovascular disease (26.0%), atrial fibrillation/flutter (22.8%), and congestive heart failure (18.9%). At baseline, 21.3% of pts had prior BTKi use, and 79.5% and 20.5% had 1 and 2+ prior lines of therapy for MCL, respectively. Concomitant prescription medications included antihypertensives (55.1%), proton pump inhibitors (PPIs; 51.2%), anticoagulants (26.0%), and antiplatelet agents (11.0%). With a median follow-up of 10.1 mo, median TTNT was 11.8 mo (95% CI, 8.3, 16.9) and median OS was 22.2 mo (95% CI: 15.4, 38.4). In this comorbid and elderly pt population, 31% remained on acala therapy and 46% were alive after 24 mo. The proportion of pts with a new event (ie, any adverse event occurring after acala initiation in pts without the event at baseline) were: atrial fibrillation/flutter (11.8%), infection (11.0%), headache (9.5%), bleeding (8.7%), arrhythmia (6.3%), and hypertension (1.6%).

Conclusions: This RW study demonstrated that, among pts with MCL who received acala in the R/R setting, effectiveness was similar to a recently presented RW evidence study utilizing EHR. Despite a pt population characterized by advanced age and high comorbidity burden, a high percentage remained on acala therapy and were alive at 24 mos. The safety profile of acala demonstrated a low number of new-onset events (especially hypertension, bleeding, and other CV events) considering an older comorbid pt population with high rates of anticoagulant and PPI use. Overall, the claims data from this study help reinforce the role of acala as an effective and safe treatment in R/R MCL.

Patel:ADC Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy; Trillium Therapeutics/Pfizer: Consultancy, Research Funding; TG Therapeutics: Consultancy, Speakers Bureau; Sunesis Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Nurix: Research Funding; Morphosys: Consultancy; Merck: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; Kite: Consultancy, Research Funding, Speakers Bureau; Genentech/Roche: Consultancy, Research Funding; Fate Therapeutics: Research Funding; Epizyme: Consultancy, Research Funding; Curis, Inc: Research Funding; CRISPR Therapeutics: Research Funding; Caribou Biosciences: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy; Adaptive Biotechnologies: Research Funding; Xencor: Consultancy, Research Funding. Teschemaker:AstraZeneca: Current Employment. Tian:Cobbs Creek Healthcare LLC: Current Employment. Pyrih:Lundbeck: Current Employment; Cobbs Creek Healthcare LLC: Ended employment in the past 24 months. Kolvenbag:AstraZeneca: Current Employment. Patel:AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Wahlstrom:AstraZeneca: Current Employment. Cui:Cobbs Creek Healthcare LLC: Current Employment.