Rituximab Concentration Varies in Patients With Different Lymphoma Subtypes and Correlates With Clinical Outcome

Shu Liu; Zhao Wang; Rongxin Chen; Xueding Wang; Xiaojie Fang; Zhuojia Chen; Shaoxing Guan; Tao Liu; Tongyu Lin; Min Huang; He Huang

doi:10.3389/fphar.2022.788824

Rituximab Concentration Varies in Patients With Different Lymphoma Subtypes and Correlates With Clinical Outcome

Front Pharmacol. 2022 Jan 26:13:788824. doi: 10.3389/fphar.2022.788824. eCollection 2022.

Authors

Shu Liu^{1

2}, Zhao Wang², Rongxin Chen³, Xueding Wang¹, Xiaojie Fang², Zhuojia Chen², Shaoxing Guan¹, Tao Liu², Tongyu Lin^{2

4}, Min Huang¹, He Huang²

Affiliations

¹ Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
² State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
³ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
⁴ Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Abstract

Individual variations in concentrations of rituximab in different B cell non-Hodgkin's lymphoma subtypes and their relevance to efficacy were still unclear. From 2016 to 2021, a prospective clinical trial was conducted, and 510 samples with 6 uncommon subtypes of B-cell lymphoma were enrolled to examine the pharmacokinetic behaviour of rituximab and its impact on clinical outcomes, including complete response (CR), progression-free survival (PFS) and overall survival (OS). Considerable variability was observed in the rituximab trough concentration in the first cycle (C_1-trough, 1.16-55.52 μg/ml) in patients with different lymphoma subtypes. Patients with "double-hit" lymphoma (4.01 ± 0.77 μg/ml) or mantle cell lymphoma (MCL; 15.65 ± 16.45 μg/ml) had much lower C_1-trough and worse outcomes. Great individual variation in the C_1-trough existed among patients with mucosa-associated lymphoma (MALT), and the high C_1-trough observed in patients treated with the RB regimen was associated with a better response than was obtained with R-CHOP (38.41 ± 14.13 μg/ml vs 15.49 ± 8.80 μg/ml, p = 0.0029). Despite the high aggressiveness of the cancer, Burkitt lymphoma patients receiving intensive chemotherapy had the highest C_1-trough (28.85 ± 9.35 μg/ml) and maintained long-term PFS. The C_1-trough in patients with mixed, unclassifiable B-cell lymphoma was close to 20 μg/ml, and these patients had acceptable outcomes. Overall, a low rituximab C_1-trough was associated with adverse consequences, including persistent progression, early recurrence and a short OS, however, some high-risk factors appeared to be balanced by the presence of a high C_1-trough. Basal levels of circulating CD19⁺ lymphocytes differed between and within patients with diverse lymphoma subtypes and were negatively correlated with C_1-trough. Therefore, the traditional doses of rituximab are inadequate for patients with "double-hit" lymphoma and MCL. Increasing the initial rituximab dose according to the disease, high-risk factors and even the baseline CD19⁺ lymphocyte count will be new methods to optimize therapeutic regimens for patients with different lymphoma subtypes.

Keywords: mantle cell lymphoma; outcomes; pharmacokinetic; rituximab; “double-hit” lymphoma.