Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature

Abstract

Primary effusion lymphoma (PEL) is a rare aggressive subset of non-Hodgkin B-cell lymphoma. It is caused by Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8). It occurs mainly, but not exclusively, in HIV-positive patients. PEL predominantly develops in serous cavities and occasionally in extracavitary regions. PEL carries a very poor prognosis with a median survival time of <6 months. Indeed, currently used treatment modalities such as CHOP chemotherapy are far from achieving complete and sustainable remission. Therefore, there is no clear standard of care established in the treatment of PEL patients, stressing the need for novel-targeted approaches. Here, we have attempted a comprehensive assessment of the treatment of PEL, discussed avant-garde therapies and updated the state of preclinical research with promising clinical applications in the field. These include inhibitors of viral replication, modulators of cell signaling and inflammation, nuclear factor kappa B (NF-κB) and histone deacetylase inhibitors, and recently the combination of arsenic trioxide and interferon-alpha. Some of these targeted therapies have not yet reached clinical studies, although others were used in a few individual case reports with low numbers of patients. We also describe the first case of a 77-year-old, HIV-negative, HHV8-positive patient diagnosed with PEL limited to the pleural and peritoneal cavities. He received lenalidomide 25 mg/day for 21 days every 28 days. Treatment was well tolerated with no side effects. He rapidly improved after 1 month of treatment and progressively achieved complete remission persistent after 18 months of therapy. We believe that this review will bridge an important gap between classical chemotherapy and modern approaches of targeted therapy. Finally, our findings warrant further evaluation of lenalidomide in future prospective clinical studies.

Primary Effusion Lymphoma: Cytological Diagnosis of a Rare Entity - Report of Two Cases in HIV-Uninfected Patients from a Single Institution

“…Due to its rarity there is no clear standard of care established in the treatment of PEL patients. Actually, targeted drugs like the proteasome inhibitors bortezomib, lenalidomide and brentuximab vedotin seem to give some hope in this field [12,13]. …”

Mechanistic Insights into Chemoresistance Mediated by Oncogenic Viruses in Lymphomas

“…Another study reported that intrapleural injection of bleomycin without any systemic therapy achieved a durable remission after pleurodesis in two HIV-seronegative patients with PEL [61]. Recently, a case report showed that after one month of lenalidomide treatment (a multi-functional agent with anti-angiogenic and anti-osteoclastogenic effects, and immunomodulatory activity), an HIV-seronegative patient with PEL significantly improved and after 18 months, complete remission persistence was progressively achieved [62]. Yet, another study reported that two PEL patients treated with oral rapamycin showed a positive clinical response and the authors postulated that KSHV+ patients who received a transplant could also benefit from substituting rapamycin for cyclosporine A and offer protection against PEL [63].…”

Current status of treatment for primary effusion lymphoma

“…It exerts its antitumor action through various mechanisms, such as activation of the immune system, inhibition of angiogenesis and direct antineoplastic effects. Treatment with lenalidomide has never been reported in PEL patients with favorable results (64). As lenalidomide was also successfully used to treat three patients with advanced refractory Kaposi sarcoma, this novel agent is expected to be used in prospective studies.…”