A revival: radioimmunotherapy in mucosa associated lymphoid tissue lymphoma

The radioimmunoconjugate ⁹⁰Y-ibritumomab tiuxetan (Zevalin; Bayer Schering Pharma, Spectrum Pharmaceuticals) has been approved in the European Union for patients with follicular lymphoma refractory to rituximab and for consolidation after achieving response in first-line chemotherapy. Radioimmunotherapy is appealing in low-grade lymphoma that is radiosensitive to low-dose radiation. In their article published in Leukemia and Lymphoma, Hoffman et al. [1] address the question of its effect on mucosa associated lymphoid tissue (MALT) lymphoma in six patients with at least three relapses or who were progressing after conventional therapy, which included rituximab. Five patients achieved complete remission, one patient achieved a partial response, and one patient became stable in disseminated disease. At the time of the report, at least two patients had more than 24 months of disease-free duration. This is a second report of the use of Zevalin in indolent extranodal lymphoma. The first report by Esmaeli et al. [2] reported front-line treatment of 12 early stage ocular adnexal lymphomas. Ten patients had complete responses, and two patients had partial responses. With a median follow up of 20 months (range 6–49 months), no cases of distant extraorbital relapse were present. In one partial responder who thereafter had progression, radiotherapy of 30 Gy by external beam radiotherapy (EBRT) was performed. Three patients had quantitative radionuclide imaging (single photon emission computed tomography/computed tomography; SPECT/CT). The estimated absorbed radiation dose to the orbital soft tissues was less than 3 Gy. Although dosimetry is difficult with Zevalin and the surrogate 111-indium, the radiation dose delivered by radioimmunotherapy is well below the threshold for significant radiation-induced ocular toxicity. The most common toxicities with Zevalin were hematological, with reversible delayed thrombocytopenia and neutropenia.

MALT lymphoma has an indolent course and a variety of clinical presentations and underlying causes. Patients with early-stage gastric MALT should first be treated with Helicobacter pylori (HP)-eradication. In non-gastric or disseminated lymphoma, the standard approach includes radiotherapy, chemotherapy with rituximab, or both. Choice of treatment is also based on the potential toxicities, and a wait-and-watch policy can be proposed in asymptomatic patients. EBRT has been the most frequently used modality to treat localized MALT or other indolent lymphoma. However, it does not address systemic sites of involvement in patients with multifocal disease and the risk of contralateral orbital relapse. As reported in this paper, three patients had multifocal disease: two on the skin and one in several organs including the stomach and the lung. In addition, EBRT for the treatment of orbital lymphoma is associated with immediate and ocular side-effects including dry-eye syndrome and cataracts. However, one can question the standard dose of 30 Gy used in EBRT; several reports demonstrated the efficacy of low-dose radiotherapy with 2 × 2 Gy, which did not induce significant side effects [3]. Several reports have demonstrated that the anti-CD20 monoclonal antibody rituximab has activity alone in MALT lymphoma [4,5]. However, when it is used as a single agent, the complete remission rate is still low, ranging from 33 to 44% [6,7], which suggests association with chemotherapy optimally but with more toxicities. Additional experience has been gained in follicular lymphoma with radioimmunotherapy. Front-line treatment with a single course of 131-iodine tositumomab [8] has been reported in 76 cases of follicular lymphoma, which resulted in 75% complete remission and 5-year progression-free survival of 59%. In the early stage, radioimmunotherapy produces MALT lymphoma response rates similar to those with EBRT; thus, it seems attractive to consider this approach a reasonable alternative to front-line treatment in selected localizations. Moreover, the use of radioimmunotherapy does not prevent the use of other subsequent treatments in cases of relapse or progression. The high response rate with long duration in relapses and in progressing patients reported here provides more robust data on the efficacy of radioimmunotherapy in MALT lymphoma. However, more patients with a longer follow-up are required to estimate the true relapse-free and progression-free survival rates, which suggests that further prospective studies should be conducted in selected non-bulky, localized stage disease.

Potential conflict of interest: A disclosure form provided by the author is available with the full text of this article at www.informahealthcare.com/lal.