Prospective trial of targeted radioimmunotherapy with Y-90 ibritumomab tiuxetan (Zevalin) for front-line treatment of early-stage extranodal indolent ocular adnexal lymphoma

Background: To determine the efficacy and side-effects of Y-90 ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). Patients and methods: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by Y-90 ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the The International Working Group response criteria. All patients had In-111 ibritumomab tixuetan imaging to confirm expected biodistribution before Y-90-Zevalin therapy; in addition, three patients had an optional single photon emission computed tomography-computed tomography scan to estimate the absorbed radiation dose to the orbital and ocular tissues. Results: The study included seven women and five men. The median age was 60 years (range 22-79). Nine patients had mucosa-associated lymphoid tissue lymphoma of conjunctiva or orbit; three patients had grades 1-2 follicular lymphoma of orbit. One patient who had been deemed stage I-E initially was found to have another lesion in her deltoid muscle on positron emission tomography 2 weeks after enrollment. She was kept on trial although her disease was reclassified as stage IV due to this single additional (biopsy-proven) site. Ten patients had a complete response and two partial response (PR) within 3 months of treatment. One patient had a recurrence in the upper eyelid 6 months after an initial PR; he then received 30 Gy of external-beam radiotherapy (EBRT). His disease later progressed again in the orbit and he is currently being considered for other treatments. A second patient who attained a PR has remained stable with no progression 12 months after treatment. With a median follow-up time of 20 months (range 6-44 months), there were no cases of distant (extraorbital) relapse. All 12 patients experienced grade I or II transient pancytopenia during the first 3 months after enrollment in the trial. There were no episodes of grade III or IV myelosuppression. The estimated absorbed radiation dose to the orbital soft tissues was < 3 Gy, 10 times lower than that with EBRT. Conclusions: Rituximab followed by Y-90 ibritumomab tiuxetan is an effective and safe front-line treatment for early-stage extranodal indolent B-cell lymphoma of the ocular adnexa.