Use of rituximab, temozolomide, and radiation in recurrent and refractory primary central nervous system lymphoma in the Philippines: a retrospective analysis

Abstract

Background: Refractory disease in primary central nervous system lymphoma (PCNSL) may occur despite adequate initial treatment. There is currently no standard of care for relapsed and recurrent PCSNL. No study to date documents using a combined regimen of radiotherapy, temozolomide, and rituximab. This study aimed to present the clinical course and outcomes of patients with recurrent or refractory disease who were given a combination of radiation, temozolomide, and rituximab.

Methods: Retrospective analysis was employed to evaluate data from recurrent or refractory PCNSL patients who were treated with radiation, temozolomide, and rituximab in two tertiary hospitals in the Philippines. Baseline demographics, treatment regimen, and outcomes were analyzed.

Results: Fifteen patients with a median age of 56 years were included, 11 with refractory disease and 4 with recurrent disease. Patients with bulky disease received either whole brain radiotherapy or partial field radiotherapy with rituximab and temozolomide given during radiation and for 6 months after radiation. Overall response rate to salvage therapy was 93.3% (14/15). Median overall survival from initial diagnosis was not reached (median follow-up: 84 months). Mortality rate was 33.3% (5/15), but only 2 out of 5 mortalities were from disease progression. There were only two reported cases of mild allergic reactions to rituximab, which did not result in treatment interruption.

Conclusion: Rituximab, temozolomide, and radiotherapy can be considered as an effective and safe salvage therapy for relapsed and recurrent central nervous system lymphoma.

Keywords: chemotherapy; primary CNS lymphoma; radiotherapy; recurrent CNS lymphoma; salvage therapy.

Figure 1.

(A) Flow of patients in the study. (B) Flow of treatment regimen given for recurrent and refractory PCNSL.

Figure 2.

Illustrated clinical course of patients with rrPCNSL indicating time to disease recurrence or progression and cognitive decline.

Figure 3.

Synergism of rituximab, temozolomide, and radiation in the treatment of primary CNS lymphoma. Rituximab acts on the CD20 receptor and induces cytotoxicity by increasing anti-tumor antigenicity, cell apoptosis by inhibiting NF-KB pathway among others, and chemosensitization by downregulating Bcl-2. Temozolomide and radiation inhibit DNA replication, evidently causing cell death. Radiation also increases tumor antigenicity through the release of tumor antigens during apoptosis. Both rituximab and radiotherapy may increase tumor cell detection through their indirect antigenic effect. Chemosensitization from rituximab and tumor irradiation may also potentiate the cytotoxicity of temozolomide. BTK, Bruton tyrosine kinase; IL-10, interleukin-10; JAK, Janus kinase; MTIC, 5-(3-methyl-1-triazene)-imidazole-4-carboxamide; NF-KB, nuclear factor KB; STAT, signal transducer and activator of transcription.