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

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.