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Rituximab immunotherapy offers new option for orbital pseudolymphoma


The anti-CD20 monoclonal antibody rituximab (Rituxan, Genentech) may be considered as a treatment option for benign orbital pseudolymphoma for patients in whom conventional modalities fail and in patients who experience tolerability issues with those treatments.


In a recently published article (Mayo Clin Proc. 2007;82:692-699), James A. Garrity, MD, and colleagues from the institution's ophthalmology and internal medicine departments described use of rituximab to treat a benign lymphoid proliferation. In a retrospective review of patients seen between Jan. 1, 1998, and Dec. 31, 2005, with a biopsy-confirmed orbital pseudolymphoma, they identified 11 patients who were treated with rituximab. Conditions in 10 (91%) patients responded, although seven patients required maintenance treatment or a repeat course after their conditions relapsed.

"Rituximab was initially developed to treat CD20+ B-cell non-Hodgkin's lymphoma (NHL), which is a malignancy. Orbital pseudolymphoma is a benign inflammatory lesion but is composed partly of reactive CD20+ B cells, which provided a rationale for attempting immunotherapy with rituximab," said Dr. Garrity, professor of ophthalmology, Mayo Medical School, Rochester, MN.

Rituximab was administered as an intravenous infusion at a dose of 375 mg/m2 once a week for 4 weeks. Response or a need for further treatment was assessed after 12 weeks.

Of the 11 patients included in the retrospective review, four received a single course of rituximab. That subgroup included the single patient in the series whose condition did not respond to rituximab, two patients who had been followed 4 to 8 months from their last infusion without evidence of condition recurrence, and one patient who developed submandibular swelling after 70 months. In the latter patient, NHL was diagnosed and responded to treatment with rituximab.

Of the seven remaining patients, conditions in two had positive but incomplete responses to the first course of rituximab, so they were given additional treatment to achieve a maximal response. The other five patients were re-treated for condition relapse.

Rituximab was administered to all patients on an outpatient basis. It was associated with minimal infusion-related toxicity. No patient required hospitalization for management, and the drug was otherwise well-tolerated.

"We had some initial concerns about an increased risk of infection with this immunotherapy, but fortunately thus far, rituximab has been associated with few side effects," said Dr. Garrity.

He told Ophthalmology Times that the index case in the series involved a patient whose tumor was minimally controlled by primary treatment with steroids. As the steroid dose was increased in an attempt to achieve a better response, steroid toxicity became an issue. Treatment with external-beam radiation therapy was started and was effective initially, but within a few months, the tumor relapsed and was even larger than when the patient was first seen.

"It was then that I consulted with my hematology colleague, Thomas E. Witzig, MD. Dr. Witzig was an investigator in early clinical trials of rituximab for NHL, and he suggested its use," Dr. Garrity explained. "The patient's response was almost immediate. While the swelling returned 9 months later, the pseudolymphoma responded to rituximab re-treatment."

He continued, "We learned from this case that rituximab was rapidly effective, but we were under the mistaken impression that it would be a one-time course." To date, however, he said, no patient's condition that initially responded to rituximab has been refractory to re-treatment for relapse.

Concomitant findings in several rituximab-treated patients included asthma and sinus symptoms. Interestingly, those features also resolved with rituximab therapy.

"In addition to discovering the efficacy of rituximab in the treatment of orbital pseudolymphoma in this case series, the response of those other features raises our interest in thinking about possible new underlying mechanisms for their development in these patients," Dr. Garrity said.

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