ASH 2025: Real-World Treatment Patterns, Patient Characteristics, and Outcomes of CBTKI-Based Therapies Amongst a Contemporary Cohort of Patients with R/R MCL in the United States

Covalent Bruton tyrosine kinase inhibitors (cBTKis) have been a cornerstone of treatment for relapsed/refractory mantle cell lymphoma (MCL) for many years, but it remains unclear how well patients respond to these therapies in real-world settings. Investigators therefore used electronic health records from the nationwide Flatiron Health database to examine outcomes for people with MCL who received cBTKi therapy in the second line or later. The results of this analysis were presented by Kami Maddocks, MD of Ohio State University Comprehensive Cancer Center, a Foundation Scientific Advisory Board (SAB) Member and member of the Foundation’s Mantle Cell Lymphoma Consortium (MCLC) Executive Committee.

The analysis included records from 745 patients with MCL who had received a median 3 lines of therapy. Most (80.5%) received their first cBTKi in the second line (16.4% in third line, 3.2% in fourth line or later). Approximately two-thirds of patients received cBTKi monotherapy as their first cBTKi treatment, of which acalabrutinib was most commonly used (33.8%; 20.1%, zanubrutinib; 13.0% ibrutinib). The median time from diagnosis to initiation of cBTKi therapy was 12.6 months, and most patients had high-risk disease characteristics at the start of treatment. The 24-month survival rate in the full group was 56.5%.

The median time from starting cBTKi therapy to the last observation or death was 13.3 months, with similar survival intervals regardless of line of therapy. The median time to next treatment (or death) was 10.8 months overall for those who received cBTKi monotherapy, but was markedly shorter for those in later lines of therapy—12.1 months for those in the second line, 7.1 months in the third line, and 3.9 months in the fourth line or later. Median time to treatment discontinuation or death was 8.0 months. These intervals were shorter in patients who received cBTKi combination therapy (median time to discontinuation, 5.9 months; median time to next treatment, 9.0 months). 

The researchers concluded that these results suggest that patients with relapsed/refractory MCL frequently have high-risk disease at the start of cBTKi therapy, and that the time from diagnosis to second line therapy or beyond is short in this population (just over a year). The poor outcomes in this population emphasize the need for improved treatment options in patients with aggressive diseases such as MCL.