Outcomes For Recurrent Mantle Cell Lymphoma Post-Btk Inhibitor Therapy In Japan: An Administrative Database Study

Objective No standard drug therapies are currently available after covalent BTK inhibitor (BTKi; ibrutinib) treatment of patients with mantle cell lymphoma (MCL). We investigated real-world treatment patterns and outcomes for MCL patients following BTKi treatment in Japan. Design Real-world data (Apr. 2008 – Sep. 2020), provided by Medical Data Vision Co. Ltd., was from a Japanese hospital-sourced administrative database. First-line (1L) therapy was the first identified use of an anti-tumor drug. Follow-up was from the initiation of 1L until the end of available data. Setting Hospital Patients Adult patients (aged ≥20 years) treated for recurrent MCL between Dec. 2010 –Sep. 2019 and who had received prior BTKi therapy. Patients not excluded: any level of existing disability. Interventions Available BTKi and other MCL therapies in Japan during the study period. Main Outcome Measures Treatment patterns, outcomes, and demographics. Results 1,203 patients (mean age 71, male 74%) received at least 1L and were included in the study population. Of these, 270 (22%) patients received BTKi (ibrutinib) at any line of therapy, with the majority receiving it as second-line (41%) or third-line therapy (21%). Of the 270 BTKi-treated patients, 183 (68%) patients discontinued this agent, and 108 (40%) subsequently received post-BTKi therapy. These 108 patients received 60 unique anti-tumor drug combinations; 27% bendamustine-based, 19% bortezomib-based, and 13% cytarabine-based. The median (95% CI) time to treatment discontinuation of post-BTKi treatments was 1.5 (1.1–2.0) months. The median (95% CI) overall survival for post-BTKi therapies was 5.5 (3.9–9.4) months. Numerically higher patient rates received blood transfusion (39% vs 15%), concomitant radiotherapy (8% vs 4%), and anti-infectives (52% vs 32%) and experienced febrile neutropenia requiring GCSF treatment (13% vs 1%) for post-BTKi vs BTKi treatments, respectively. Atrial fibrillation/flutter (5% vs 10%) rates were lower for post-BTKi than BTKi (ibrutinib) treatment. Conclusions Patients with MCL who have been previously treated with BTKi subsequently experience extremely poor outcomes with currently available therapy options. The development of safe and effective targeted therapy after BTKi is needed to improve the otherwise dismal outcomes of these patients.