Researchers affiliated with the NCI-sponsored New Approaches to Brain Tumor Therapy (NABTT) consortium have reported that intravenous Rituxan® (rituximab) may be effective in the treatment of primary central nervous system lymphoma (PCNSL). These results were presented at the 2008 annual meeting of the American Society of Clinical Oncology in May, 2008.¹

Primary central nervous system lymphoma is a relatively uncommon form of non-Hodgkin’s lymphoma (NHL) that has been increasing in incidence during the past three decades. Unlike the progress made in the general treatment of NHL, there has been little progress in the treatment of PCNSL NHL. The standard treatment is high-dose methotrexate and whole-brain radiotherapy, which has improved outcomes. However, treatment-related neurotoxicity is common, especially in the elderly who often have poor renal function. Currently, there is no optimal treatment of elderly patients with PCNSL NHL. Attempts have also been made to disrupt the blood-brain barrier with osmotic agents such as mannitol. Recent studies have found that the combination of Temodar® (temozolomide) and Rituxan was an effective treatment regimen for patients with PCNSL (see related news).

There is emerging evidence that Rituxan administered intrathecally or intravenously alone or in combination with other agents can be effective in treating PCNSL and related CNS diseases. For example, studies have found that lymphomatoid granulomatosis involving the CNS can be treated successfully with intravenous Rituxan.² A recent study has also has also shown that combining Rituxan with methotrexate allows for reduced doses of CNS radiotherapy for the treatment of PCNSL.³ Furthermore studies have suggested that Zevalin® (Yttrium-90 ibritumomab tiuxetan) is also effective in treating PCNSL.⁴

The study presented at ASCO 2008 involved nine patients with PCNSL who had failed other therapies. Two patients had a partial response, and one patient had a complete response. Responses lasted 174 to 228 days in two patients, and response persists in the third patient at 324 days of observation. Side effects were minimal. Cancer has regressed in one-third (three) of patients, with one patient achieving a complete disappearance of detectable cancer.

These researchers concluded that Rituxan used alone for patients with PCNSL that does not respond to standard therapies may provide effective treatment for some patients, as regression of cancer was achieved in one-third of patients. The authors state that treatment with Rituxan warrants further study in combination with other chemotherapy agents; they add, “Maintenance [Rituxan] is well tolerated and may improve disease control in this patient population.” Further enrollment and follow-up for this trial are ongoing.

Comments: These data, taken together, suggest that Rituxan and other anti-CD20 antibodies penetrate the blood-brain barrier and provide effective treatment for PCNSL.

Related News:

High-Dose Chemotherapy, Autologous Transplant and Whole Brain Radiation Effective for Primary CNS Lymphoma (08/21/2006)

Rituxan® plus Temodar® Effective for Primary Central Nervous System Lymphoma (05/31/2005)

Chemotherapy and Radiation Therapy Required for Primary Brain Lymphoma (12/20/2002)

Reference:

[1] Batchelor T, Lesser G, Grossman S, et al. Rituximab monotherapy for relapsed or refractory primary central nervous system lymphoma. Proceedings from the 2008 annual meeting of the American Society of Clinical Oncology. Abstract #2043.

[2] Ishiura H, Morikawa M, Humada M, et al. Lymphomatoid granulomatosis involving central nervous system successfully treated with rituximab alone. Archives of Neurology. 2008;65:662-665.

[3] Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. Journal of Clinical Oncology. 2007;25:4730-4735.

[4] Doolittle ND, Jalinske K, Belanger R, Study of radiolabeled indium-111 and yttrium-90 ibritumomab tiuxetan in primary central nervous system lymphoma. Leukemia Lymphoma. 2007;110:2538-2534.