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Systemic anti-CD20 (rituximab) as primary treatment for symptomatic primary uveal lymphoma.

ABSTRACT: Purpose:Uveal lymphomas are indolent, frequently choroid-involving neoplasms that are mainly CD20-positive B-cell extranodal marginal zone lymphoma. Irreversible visual loss may occur from retinal detachment and/or glaucoma among untreated symptomatic patients, or from radiation-induced changes secondary to external beam radiotherapy. To avoid radiation-induced complications, we used systemic rituximab monotherapy as primary treatment, and present two cases to show its long-term effectiveness for symptomatic primary uveal lymphoma. Observations:Two elderly men who presented with painless blurred vision were clinically diagnosed with symptomatic primary uveal lymphoma, which were biopsy-confirmed to be marginal zone lymphoma. Both patients with symptomatic, primary marginal zone uveal lymphoma that appeared as multiple yellow, nummular choroidal infiltrates, had complete ocular remission after three and one cycles of systemic rituximab monotherapy (375mg/m2 infused intravenously once weekly for four consecutive weeks), with disappearance of the lesions and improvement of visual acuity. Both patients tolerated systemic monotherapy well without any adverse systemic or ocular effects. There was no local ocular recurrence at 29 and 39 months after the last treatment. Conclusions:and Importance: Systemic rituximab monotherapy induced complete ocular remission and improved visual acuity, without adverse effects, and without local ocular recurrence of uveal lymphoma 29-39 months following the last treatment. To our knowledge, this is the first manuscript to show long-term effectiveness of systemic rituximab monotherapy as the primary treatment for symptomatic primary uveal lymphoma. Long-term follow-up of this indolent neoplasm is still imperative to monitor its ocular and systemic course.

SUBMITTER: Tiu Teo HM

PROVIDER: S-EPMC6586989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rituximab, a murine-human chimera, is the first monoclonal antibody (mAb) developed as a therapeutic agent to target CD20 protein. Its Fab domain and its interaction with CD20 have been extensively studied and high-resolution atomic models obtained by X-ray diffraction or cryo-electron microscopy are available. However, the structure of the full-length antibody is still missing as the inherent protein flexibility hampers the formation of well-diffracting crystals and the reconstruction of 3D microscope images. The global structure of rituximab from its dilute solution is here elucidated by small-angle X-ray scattering (SAXS). The limited data resolution achievable by this technique has been compensated by intensive computational modelling that led to develop a new and effective procedure to characterize the average mAb conformation as well as that of the single domains. SAXS data indicated that rituximab adopts an asymmetric average conformation in solution, with a radius of gyration and a maximum linear dimension of 52 Å and 197 Å, respectively. The asymmetry is mainly due to an uneven arrangement of the two Fab units with respect to the central stem (the Fc domain) and reflects in a different conformation of the individual units. As a result, the Fab elbow angle, which is a crucial determinant for antigen recognition and binding, was found to be larger (169°) in the more distant Fab unit than that in the less distant one (143°). The whole flexibility of the antibody has been found to strongly depend on the relative inter-domain orientations, with one of the Fab arms playing a major role. The average structure and the amount of flexibility has been studied in the presence of different buffers and additives, and monitored at increasing temperature, up to the complete unfolding of the antibody. Overall, the structural characterization of rituximab can help in designing next-generation anti-CD20 antibodies and finding more efficient routes for rituximab production at industrial level.

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Systemic anti-CD20 (rituximab) as primary treatment for symptomatic primary uveal lymphoma.

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