Response of AIDS-related plasmablastic lymphoma (PBL) to bortezomib

Abstract

e19562 PBL are a group of highly aggressive neoplasms originally described in the oral cavity and jaws of HIV-infected patients. An AIDS-defining illness, PBL comprises 2.6% of AIDS-related lymphomas. PBL are best distinguished by their unique immunophenotype. They are terminally differentiated B-cell neoplasms, and typically lack common B-cell markers but uniformly express plasma cell markers. We report the first case of PBL that responded to bortezomib. A 42-year-old male with newly diagnosed AIDS presented with nausea, vomiting, bloody diarrhea and epigastric pain. EGD with biopsy revealed a high-grade PBL of the stomach. Flow cytometry was negative for CD45 and all common epithelial, T-cell and B-cell markers, but was positive for CD138 and p63(VS38c). Karyotyping revealed t(8;14), amongst other abnormalities. PET/CT showed significant hypermetabolism in multiple thoracic and abdominal lymph nodes, the left lung, liver and several bones. The diagnosis was stage IVBE PBL. Highly active anti-retroviral therapy was begun. Anthracycline-based chemotherapy was avoided due to persistent hyperbilirubinemia. Bortezomib was then administered at a dose of 1.3 mg/m2 IV on days 1, 4, 8 and 11. PET/CT on day 7 showed a marked decrease in hypermetabolism after only 2 doses, signifying a dramatic treatment response. After a total of 4 doses of bortezomib, he unfortunately succumbed to severe septic shock before a repeat PET/CT could be obtained. The prognosis of PBL is poor, with a median survival of about 6 months in most series. The WHO classifies PBL as a variant of diffuse large B-cell lymphoma. Accordingly, CHOP and CHOP-like regimens have mostly been used. However, studies of their immunophenotype and molecular histogenesis suggest that PBL are more closely related to plasma cell neoplasms. Bortezomib is a proteasome inhibitor widely used in multiple myeloma and mantle cell lymphoma. We chose bortezomib based on our patient's poor performance status and immune function, the desire to avoid combination chemotherapy, and translocations involving the immunoglobulin heavy chain gene locus (8;14) similar to those seen in multiple myeloma(4;14, 14;16) and mantle cell lymphoma(11;14). A shift in the paradigm of treatment of PBL towards agents effective in plasma cell malignancies may be necessary. [Table: see text]