Outcomes for Patients with Mantle Cell Lymphoma Post-Covalent BTK Inhibitor Therapy in the United States and Japan: A Study of Two Real-World Databases
Authors: Rai Shinya , Hess Lisa M. , Chen Yongmei , Bowman Lee , Abada Paolo B. , Konig Heiko , Walgren Richard A. , Tanizawa Yoshinori , Cai Zhihong , Tajimi Masaomi 
Published: November 2021

Abstract
Background: Patients with mantle cell lymphoma (MCL) have limited treatment options following covalent BTK inhibitor (cBTKi) therapy, with no standard regimens defined. The aim of this study was to investigate real-world treatment patterns and the outcomes for patients with MCL following cBTKi treatment utilizing two separate datasets - one from the US and one from Japan.
Methods: De-identified patient-level electronic medical record data from two real-world databases (ConcertAI in the US and Medical Data Vision in Japan) were utilized for this study. Eligible patients were ≥18 years old and were diagnosed with MCL between January 2010 and Oct 2019 in the US, or between Dec 2010 and Sept 2019 in Japan. Data were available through 2020 to allow a minimum of 1 year of follow-up for all patients. Patients were required to have completed treatment with at least one cBTKi during the 1st-3rd lines of therapy. Time-to-event analyses utilized the Kaplan-Meier method.
Results: 303 US patients (median age 70.6 years, male 74.6%) and 150 Japanese patients (median age 77 years, male 73.3%) met eligibility criteria. 142 (46.9%) patients in the US and 79 (52.7%) in Japan received subsequent post-cBTKi therapy. The remaining 161 (53.1%) in the US and 71 (47.3%) in Japan did not receive further treatment. In the US, immediate post-cBTKi regimens included chemotherapy (n=85, 59.9%) and additional cBTKi-based (n=40, 28.2%), or BCL2i-based (n=17, 12.0%) therapy. In Japan, immediate post-cBTKi regimens were nearly exclusively chemotherapy-based (n=70, 88.6%), and only 9 (11.4%) patients were retreated with cBTKi-containing regimens. Median time from the end of cBTKi therapy to discontinuation of the immediate post-cBTKi therapy or death was 3.8 months (n=303, 95% CI: 2.6-5.4) in the US and 2.3 months (n=150, 95% CI: 1.5-3.0) in Japan. Among those who received post-cBTKi therapy, the duration of therapy was 2.7 months (n=142, 95% CI: 1.9-3.5) in the US and 1.8 months (n=79, 95% CI: 1.1-2.5) in Japan. Median overall survival from discontinuation of cBTKi therapy was 8.2 months (n=303, 95% CI: 6.1-17.4) in all US patients and 5.6 months (n=150, 95% CI: 3.8-10.4) in all Japanese patients.
Conclusion: Patients with MCL previously treated with cBTKi experience very poor outcomes, as measured by their duration of subsequent therapy and overall survival. Data were generally consistent between the US and Japan. The development of new safe and effective therapies after cBTKi is needed to address the growing unmet medical need in this treatment setting.

Disclosures
Rai: Janssen Pharmaceutical: Speakers Bureau; Ono Pharmaceutical: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau. Hess: Eli Lilly and Company: Current Employment. Chen: Eli Lilly and COmpany: Current Employment, Current holder of stock options in a privately-held company. Bowman: Eli Lilly and Company: Current Employment, Current holder of stock options in a privately-held company. Abada: Eli Lilly and Company: Current Employment, Current holder of stock options in a privately-held company. Konig: Eli Lilly and Company: Current Employment. Walgren: Eli Lilly and Company: Current Employment, Current holder of individual stocks in a privately-held company. Tanizawa: Eli Lilly Japan K.K.: Current Employment, Current holder of stock options in a privately-held company. Cai: Eli Lilly Japan K.K.: Current Employment. Tajimi: Eli Lilly Japan K.K.: Current Employment.