Title:Targeted Strategies in the Treatment of Primary Gastric Lymphomas: From Rituximab to Recent Insights into Potential New Drugs
Volume: 21
Issue: 8
Author(s): Francesca Merchionne, Pasquale Iacopino, Carla Minoia, Angela Iacobazzi, Antonio Rana, Simona Serrati, Giacoma De Tullio, Giacomo Loseto, Angela Lapietra, Annunziata Lucarelli and Attilio Guarini
Affiliation:
Keywords:
Bortezomib, diffuse large B-cell lymphoma, eradication therapy, Helicobacter pylori, MALT lymphoma, pathogenesis,
stomach, rituximab, targeted therapies, 90Y-Ibritumomab tiuxetan.
Abstract: Primary gastric non-Hodgkin’s lymphomas (PG-NHL) are the most common extranodal lymphomas, representing
between 47% and 74% of all gastrointestinal lymphoma cases. In Western countries two histological types, diffuse
large B-cell (DLBC) NHL and mucosa-associated lymphoid tissue (MALT) NHL, are more frequently represented, accounting
for the majority of gastric tumors after adenocarcinoma. For several years treatment of these PG lymphomas
consisted of surgery, chemotherapy and radiotherapy, alone or in combination. In the last two decades however, advances
in our understanding of their pathogenesis and biology have changed the treatment strategy, at least as regards the early
stages of disease. In addition to making tumor regression possible through the eradication of Helicobacter pylori, which is
considered the main pathogenic agent, this understanding has also provided a solid rationale to assess the efficacy of targeted
therapy, namely of drugs which interfere with specific molecules expressed by tumor cells or are involved in key
growth pathways of these lymphomas. In particular, rituximab, a monoclonal anti-CD20 antibody, radioimmunotherapy,
the first-generation proteasome inhibitor bortezomib and lenalidomide have been evaluated. Despite significant antitumor
activity in this subset of NHL and manageable toxicity, many questions still remain however about the optimal dose, the
best administration schedule and their combination with conventional chemotherapy. This review focuses on the pathogenesis
of PG-MALT and DLBC lymphomas, and discusses the results of clinical trials on the impact of new agents on
prognosis and survival in these patients, considering also potential new therapautic targets.
