TREATMENT STRATEGIES FOR MALIGNANT LYMPHOMA BASED ON BIOMARKERS

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Abstract

Malignant lymphoma consists of a number of types of diseases as described in WHO classification. Recent treatment strategies for malignant lymphoma are based on disease entities or biomarkers. Rituximab is a chimeric monoclonal antibody (MoAb) drug targeting CD20, and widely used for CD20-positive B-cell malignancies. Thus discrete strategies are now adopted for B-cell and T-cell malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and rituximab-CHOP (R-CHOP) has been established as a standard therapy for DLBCL. Rituximab-containing chemotherapies as well as rituximab-maintenance therapy have improved the prognosis of follicular lymphoma. Nowadays rituximab-containing treatments are widely applied for the management of CD20-positive lymphoid neoplasms. A number of MoAbs other than rituximab have been developed for B-cell malignancies. For examples, radioisotope-conjugated anti-CD20 MoAbs, novel anti-CD20 MoAbs, antibody-drug conjugates (ADC) targeting CD22, and anti-CD52 MoAb. Down-regulation of target antigen expression after MoAb therapy such as rituximab has been reported, and heterogeneous expression patterns are frequently observed in various types of the diseases and clinical conditions. It is important to clarify the mechanisms of loss of antigen expression after MoAb therapy, relationship between antigen expression and the effect of MoAb treatment, and the ways to enhance the effect of MoAb therapy in these conditions. T- and NK-cell lymphoma generally shows poorer prognoses and development of novel treatment is vital. Recently, anti-CCR4 antibody has been developed and showed significant clinical activities for adult T-cell leukemia/lymphoma (ATL). SMILE is a novel combination chemotherapy that is effective for NK/T-cell lymphoma, nasal type, which frequently shows multidrug resistant. Brentuximab vedotin is an ADC targeting CD30 and effective in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma. Novel treatments based on biomarkers will lead to further improvement in the treatment of malignant lymphoma in the future.

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