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CD4 counts and the risk of systemic non-Hodgkin's lymphoma in individuals with HIV in the UK.

ABSTRACT: Since the introduction of highly active antiretroviral therapy, there has been a decline in the incidence of non-Hodgkin's lymphoma among HIV-infected individuals. We described trends in the incidence of systemic non-Hodgkin's lymphoma in the UK CHIC Study from 1996-2006 and evaluated the association between immunosuppression and development of systemic non-Hodgkin's lymphoma: 286/23,155 (1.2%) individuals developed an AIDS-defining lymphoma (258 systemic). Younger age, receipt of highly active antiretroviral therapy and later calendar year were all independently associated with a reduced risk of systemic non-Hodgkin's lymphoma. A lower latest CD4 count was strongly associated with systemic non-Hodgkin's lymphoma, in patients who had (RR per log(2)(cells/mm(3)) higher: 0.62) and had not (0.70) received highly active antiretroviral therapy. Associations with other measures of immunosuppression, including nadir CD4 count, experience and duration of severe immunosuppression, were generally weaker. Earlier highly active anti-retroviral therapy initiation and wider access to HIV testing is advocated to reduce the risk of systemic non-Hodgkin's lymphoma.

SUBMITTER: Bower M

PROVIDER: S-EPMC2688582 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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CD4 counts and the risk of systemic non-Hodgkin's lymphoma in individuals with HIV in the UK.

Bower Mark M Fisher Martin M Hill Teresa T Reeves Iain I Walsh John J Orkin Chloe C Phillips Andrew N AN Bansi Loveleen L Gilson Richard R Easterbrook Philippa P Johnson Margaret M Gazzard Brian B Leen Clifford C Pillay Deenan D Schwenk Achim A Anderson Jane J Porter Kholoud K Gompels Mark M Sabin Caroline A CA

Haematologica 20090331 6

Since the introduction of highly active antiretroviral therapy, there has been a decline in the incidence of non-Hodgkin's lymphoma among HIV-infected individuals. We described trends in the incidence of systemic non-Hodgkin's lymphoma in the UK CHIC Study from 1996-2006 and evaluated the association between immunosuppression and development of systemic non-Hodgkin's lymphoma: 286/23,155 (1.2%) individuals developed an AIDS-defining lymphoma (258 systemic). Younger age, receipt of highly active ...[more]

PMID: 19336735

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Project description:BackgroundNon-Hodgkin's lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.MethodsWe conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.ResultsWe identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200?mg intravenously every 3 weeks, three received pembrolizumab 200?mg intravenously every 4 weeks plus pomalidomide 4?mg orally every day for days 1-21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95%?CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2-3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.ConclusionsTreatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

Dataset Information

CD4 counts and the risk of systemic non-Hodgkin's lymphoma in individuals with HIV in the UK.

Publications

CD4 counts and the risk of systemic non-Hodgkin's lymphoma in individuals with HIV in the UK.

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