Diffuse Large B-Cell Lymphoma (DLBCL) is a type of blood cancer that that develops from B cell precursors. Healthy B cells produce a broad range of infection-fighting antibodies, making them indispensable for robust immune system function. B-cell lymphoma cells arise from a single precursor and are monoclonal, meaning they produce only one antibody and eventually outcompete healthy B cells. DLBCL is the most common type of non-Hodgkin lymphoma worldwide. Fortunately, therapies for this type of lymphoma are highly effective, with a 12-month overall survival rate of 75% in high-income countries.
The high survival rate of patients with DLBCL can largely be attributed to rituximab, a monoclonal antibody therapy that works by recognizing a surface marker called CD20 on malignant B-cells and recruiting other immune cells to fight the cancer. Monoclonal antibody therapies like Rituximab are typically used alongside traditional chemotherapy regimens to boost a patient’s native immune response to more effectively kill cancer cells. The efficacy boosts from monoclonal antibodies are substantial—for DLBCL treated without rituximab, the 12-month overall survival rate is only 50%.
Despite the availability of rituximab in high-income countries for more than 25 years, this type of therapy is not widely available globally. Particularly in resource-limited areas, monoclonal antibody infusions are unavailable to patients for several reasons. Setting aside their hefty price tags, antibody therapies like rituximab require long infusion times: rituximab is typically delivered intravenously, and these infusions can take 6-8 hours to complete. “That requires a lot of time to do, and it also requires an infusion suite,” says Dr. Manoj Menon, corresponding author of a recent study from Fred Hutch. Doctors in resource-limited countries have massive caseloads, making these long infusions impractical. Infusion suites also may not be readily available in low-income countries or remote areas of high-income countries. Intravenous administration of this treatment is also associated with adverse infusion reactions that under-resourced hospitals may be unable to deal with.
To overcome these limitations, researchers tested an injectable subcutaneous form of rituximab that can be administered to patients in less than 10 minutes. In trials in the US and Europe, subcutaneous rituximab has been shown to be just as effective as the intravenous form and to have a better safety profile in patients. Importantly, patients who receive rituximab strongly prefer subcutaneous administration to intravenous administration. Whether these benefits persist in resource-limited settings remained unclear. “There was a concern…that we should be doing the trials in the populations that we’re actually serving,” says Menon. Differences in environmental, nutritional, or infectious factors could all impact the outcomes associated with subcutaneous rituximab.
To address this question, researchers at Fred Hutch teamed up with physician-scientists at the Uganda Cancer Institute to conduct a clinical trial comparing subcutaneous and intravenous rituximab administration. To do this, they enrolled 18 Ugandan DLBCL patients in the trial. Six of the patients received one dose of intravenous rituximab and five doses of subcutaneous rituximab, and twelve patients received all six of their doses in the subcutaneous format. Both treatment groups reported mild adverse events including neutropenia, gastritis, and dizziness, but none of these reactions caused the patients to discontinue treatment. Of the patients that completed the treatment, 93% of them achieved complete remission, and the one-year overall survival rate was 83%, indicating that the subcutaneous rituximab treatment was effective in this population. “In this study…we showed that a country with limited resources like Uganda could achieve the same rates of overall survival that a resource-abundant country has. Ideally geography does not dictate the opportunities and access to these medications,” says Menon.
In the future, the team hopes to work to improve access to these medications. This study demonstrated that they are safe and effective, a step that will hopefully drive demand for the products to increase production and accessibility.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium members Drs. Manoj Menon and E Houston Warren and contributed to this study.
Menon MP, Ddungu H, Mubiru KR, Adams SV, Asea J, Namagembe R, Namuli P, Kambugu J, Towlerton AMH, Puronen C, Uldrick TS, Orem J, Warren EH. 2025. Phase I Study of Subcutaneous Rituximab Hyaluronidase Combined With CHOP Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma in Uganda. JCO Glob Oncol. 11:e2400489. doi: 10.1200/GO-24-00489.
Kelsey Woodruff is a PhD candidate in the Termini Lab at Fred Hutch Cancer Center. She studies how acute myeloid leukemia cells remodel the sugars on their membranes to reprogram cancer cell signaling. Originally from Indiana, she holds a bachelor's degree in Biochemistry from Ball State University. Outside of lab, you can find her crocheting and enjoying the Seattle summers.
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