Rituximab-temozolomide-radiation combo shows promise in recurrent primary CNS lymphoma

Use of rituximab, temozolomide, and radiation appears safe and effective as salvage therapy for patients with recurrent or refractory primary central nervous system (CNS) lymphoma, according to a study in the Philippines, the results of which were presented at the recent AAN 2023.

“Refractory disease in primary CNS lymphoma may occur despite adequate initial treatment,” said the researchers, led by Almira Doreen Abigail Apor from the Department of Neuroscience, University of the Philippines – Philippine General Hospital, Manila, Philippines. “There is currently no standard of care for relapsed and recurrent primary CSN lymphoma.”

Apor and her colleagues conducted this retrospective analysis to determine the clinical course and outcomes of patients with recurrent or refractory disease who received a combination of radiation, rituximab, and temozolomide.

The research team assessed data from recurrent or refractory primary CNS lymphoma patients who received the combination treatment in two tertiary hospitals in the Philippines. They also analysed baseline demographics, treatment regimen, and outcomes in this cohort.

Fifteen patients (median age 56 years) were enrolled in this study, of whom 11 had refractory disease and four had recurrent disease. Those with bulky disease underwent whole brain radiotherapy or partial field radiotherapy with rituximab and temozolomide, given during and for 6 months after radiation. [AAN 2023, abstract P13.006]

Fourteen of 15 patients (93.3 percent) showed response to salvage therapy, but the median overall survival from initial diagnosis was not reached (median follow-up 84 months). Five patients succumbed to the disease, which corresponded to a mortality rate of 33.3 percent. However, only two of these deaths resulted from disease progression.

Poor responders

A 2004 study by Plotkin and colleagues, who assessed the efficacy of repeat administration of high-dose methotrexate (HD-MTX) in the treatment of recurrent primary CNS lymphoma, reported a response rate of 87 percent (complete response, 73 percent; partial response, 14 percent), with an overall survival of 61.9 months. [Clin Cancer Res 2004;10:5643-5646]

“In our study, however, after failing to respond to a rechallenge with HD-MTX, all the patients were considered poor responders to MTX, which prompted introduction of a new treatment regimen,” the researchers said.

The National Comprehensive Cancer Network guidelines recommend the following treatment options for patients with recurrent disease: systemic chemotherapy, radiotherapy with or without chemotherapy, or HD-MTX therapy with stem cell rescue. [Biomark Res 2021;9:32]

In terms of adverse events, only two patients reported mild allergic reactions to rituximab, but these effects did not lead to treatment interruption.

“We conclude that the combination of radiotherapy, rituximab, and temozolomide is a safe and effective regimen among patients with recurrent and refractory primary CNS lymphoma,” according to Apor and her colleagues.

“Given the documented outcomes from this review, we believe that this treatment regimen should be strongly offered and considered among patients who relapse or progress with the disease,” the researchers said.

“Ultimately, the management should be multidisciplinary, individualized, and based on current available evidence,” they added.