Real-world characteristics, treatment patterns, and outcomes of patients with mantle cell lymphoma (MCL) after receiving covalent bruton tyrosine kinase inhibitors (cBTKi) in China

Abstract Introduction: MCL is an uncommon, aggressive subtype of B-cell non-Hodgkin lymphoma, associated with poor outcomes and limited response to chemotherapy. cBTKis have emerged as effective treatments for MCL; four are currently approved for relapsed/refractory MCL in China. However, a high proportion of patients develop resistance and toxicity to cBTKi, and consensus on the optimal treatment for MCL after cBTKi failure is lacking. This study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients with MCL who received cBTKi. We focus on the period following cBTKi discontinuation among Chinese patients, using a real-world database. Methods: Data were abstracted from the medical records of adults (≥18 years) first diagnosed with MCL between January 2013 and January 2024 who subsequently received cBTKi at 53 Chinese hospitals in the National Anti-Tumor Drug Surveillance System database. Demographics, clinical characteristics, and treatment patterns of patients who received cBTKi and those who received subsequent therapy after discontinuation of cBTKi were summarized using descriptive statistics. Progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and time to next treatment discontinuation (TTNTD) were assessed for patients who received post-cBTKi therapy, using the Kaplan–Meier method. Those with unknown post-cBTKi therapy start time, documented progression events with incomplete date, or death records inconsistent with start time of post-cBTKi therapy were excluded. A subgroup analysis excluding patients who had participated in clinical trials of post-BTKi therapy was conducted. Results: A total of 3114 patients who received cBTKi for MCL were included in the analysis, of whom 844 received post-cBTKi therapy. The median (interquartile range [IQR]) age at diagnosis was 62.0 (54.0–68.0) years (n=3114), with 61.1% (n=1901/3114) aged <65 years; 76.7% (n=2389/3114) were male. Most patients were diagnosed with classic type MCL (87.4%, n=2723/3114), 46.8% of those with non-missing data (n=594/1268) had low-risk disease per the Simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI), and most had Ann Arbor stage IV disease (72.2%, n=1524/2110) and Ki67 ≥30% (65.2%, n=1612/2471). Demographics and disease characteristics were broadly comparable in patients who received post-cBTKi therapy. The three most common initial cBTKi regimens among all patients were combination with anti-CD20 therapy ± chemotherapy (51.5%, n=1605/3114), monotherapy (21.9%, n=682/3114), and with anti-CD20 therapy plus other novel agents (15.7%, n=490/3114). Overall, 60.1% (n=1872/3114) received initial cBTKi as 1st line therapy; the remainder received it in 2nd line (30.1%), 3rd line (6.5%), or ≥4th line (3.3%). Among those who received post-cBTKi therapy (n=844), the most common therapies included cBTKi in combination with anti-CD20 therapy ± chemotherapy (19.4%, n=164/844), anti-CD20 therapy ± chemotherapy (16.2%, n=137/844), and cBTKi monotherapy (15.5%, n=131/844). The median (95% confidence interval [CI]) PFS among patients who received post-BTKi therapy was 7.8 (7.0–9.0) months (n=663), and OS was 16.6 (14.1–19.4) months (n=672). The median (95% CI) DOT was 5.4 (4.5–5.9) months (n=659), and TTNTD was 8.8 (7.7–11.0) months (n=551). After exclusion of those who had participated in a clinical trial of post-cBTKi therapy, the median (95% CI) PFS and OS were 7.7 (6.6–9.0) months (n=530) and 14.1 (12.3–16.6) months (n=539), respectively. The median (95% CI) DOT and TTNTD were 5.6 (4.7–6.8) months (n=528) and 10.0 (8.1–12.0) months (n=443), respectively. Conclusion: This study represents a large real-world analysis of patients with MCL treated with cBTKi in China. Most patients were aged <65 years at MCL diagnosis and received 1st line cBTKi. Post-cBTKi therapy choices were diverse, with frequent cBTKi retreatment and conventional chemotherapy noted during a period when few alternative therapies were available for patient care. The suboptimal clinical outcomes of existing post-cBTKi therapies highlight the need for more effective strategies. Funding: Eli Lilly and Company. Acknowledgements: Medical writing support was provided by Phoebe Kennedy, MSc, at Rude Health Consulting Ltd., and was funded by Eli Lilly and Company.