Pharmacokinetic assessment of subcutaneous rituximab hyaluronidase among Ugandan adults with CD20+ diffuse large B-cell lymphoma

Abstract

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy worldwide. In high-income countries, treatment outcomes for NHL have dramatically improved over the past 25 years in large parts due to rituximab. However, these same benefits have not been realized in low- and middle-income countries given limited access to monoclonal antibodies. To assess the pharmacokinetic profile of subcutaneous rituximab (sqR) among patients in Uganda, we enrolled 18 newly diagnosed patients with CD20 + diffuse large B-cell lymphoma. In cohort 1 (n = 6) IV rituximab was given on day 1 of cycle 1, followed by CHOP (cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone) chemotherapy and then sqR and CHOP for cycles 2 to 6. The second cohort (n = 12) received sqR plus CHOP for all cycles. We assessed trough concentrations (C trough ) from the plasma, and pharmacokinetic assessments were determined using an enzyme-linked immunosorbent assay. C trough was analyzed descriptively. We demonstrate that C trough provides exposure within the published reference range, was consistent across cohorts and within acceptable limits, and supports the use of sqR in Uganda. Efforts to increase access to monoclonal antibodies, including rituximab, are necessary to reduce health disparities. Subcutaneous formulations are one way forward. This trial was registered at www.clinicaltrials.gov as NCT03864419 .