Bevacizumab for recurrent primary central nervous system lymphoma: a new treatment?

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm with an incidence of 0.7 per 100 000 person-years.¹ High-dose methotrexate (HD-MTX) has been adopted as a standard of care as a single agent or in combination with other chemotherapy.^2–5 No standard therapy exists at relapse, but options include a rechallenge of HD-MTX, radiation therapy, stem cell transplant, and other chemotherapeutic agents.^2,3,6 We present the case of a patient with PCNSL and multiple recurrences, despite several lines of therapy, who had a durable response to bevacizumab; this case has not been previously reported.

A 50-year-old right-handed man presented to an outside hospital in April 2010 with unremitting headaches and difficulties with typing and balance. Noncontrast CT scan and MRI of the brain revealed a large right parietal lobe mass. The patient underwent near-gross total resection of the mass, which was consistent with diffuse large B-cell lymphoma, and a standard systemic workup for lymphoma was negative.

The diagnosis was PCNSL, and he was treated with 4 cycles of HD-MTX. Follow-up MRI revealed persistent disease and a new mass. He was then treated with whole brain radiation therapy to a dose of 45 Gy. Follow-up MRI and positron emission tomography scan showed no evidence of disease. He transferred his care to our institution, where he was treated with 2 cycles of rituximab, ifosfamide-carboplatin-etoposide (ICE), and then autologous stem cell transplant in February 2011 with busulfan and thiotepa. He was disease free until January 2012, when an MRI demonstrated disease recurrence in the brain and a small focus in the cervical spine. Cytarabine and rituximab were begun, with disease progression in the brain 2 months later. Pemetrexed and ICE were started, but a new lesion developed in the posterior body of the corpus callosum after 4 cycles. The lesion was treated with radiosurgery and a fifth cycle of ICE. The patient's disease remained stable for 6 months, when an MRI showed disease progression with enlargement of the initial lesion in the corpus callosum, a second lesion in the corpus callosum, and numerous additional enhancing lesions in the cerebellum, which were in areas of previous disease.

Given limited treatment options, the patient was started on bevacizumab 10 mg/kg on April 11, 2013. A month following the administration of bevacizumab, the MRI showed dramatically decreased enhancement of the corpus callosum masses, decrease in size and enhancement of essentially all of the cerebellar lesions, and improved right hemisphere vasogenic edema. Bevacizumab was continued every 2 weeks for 6 months with continued resolution of the disease until a complete response was noted. Given the complete response noted on the November 2013 MRI, treatment intervals were increased to every 3 weeks, then 4 weeks, and then 6 weeks, which was his schedule until therapy was stopped in June 2014 (Fig. 1). Since treatment has been discontinued, he has had multiple cerebrovascular complications but no evidence of recurrent tumor.

Fig. 1.

Postcontrast T1 MRI of the brain prior to bevacizumab treatment in April 2013 (top images). Postcontrast T1 MRI of the brain after bevacizumab treatment showing a complete response in June 2014 (bottom images).

Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor A and is FDA approved in the United States for metastatic colorectal cancer, metastatic renal cell carcinoma, non–small cell lung cancer, and glioblastoma. This is the first report of bevacizumab use in PCNSL, but there are data for its use in diffuse large B-cell lymphoma and follicular lymphoma.^7,8 The response to bevacizumab in our patient suggests that it might be considered for patients with limited treatment options and be further evaluated in a larger cohort of relapsed PCNSL patients.

Conflict of interest statement. KN, LIG: None declared. JR: Speakers Bureau-Genentech; Advisory Boards: Genentech, Novartis, Stemline, Midatech, Agenus, Novocure, Proximagen, AbbVie, Foundation Medicine, BMS. Research support: Genentech, Novartis, Stemline, MedImmune.