Impact of HIV on Clinical Presentation and Outcomes of Individuals with Multiple Myeloma

Introduction:

HIV infection and the resulting immunodeficiency predispose individuals to various plasma cell disorders including reactive plasmacytosis, monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plamacytomas. Studies have demonstrated nearly 4.5-fold increased risk of MM in HIV-infected (HIV+) individuals. Limited evidence from case reports/small series of MM in HIV+ patients have suggested a younger age at presentation, more disseminated disease, an aggressive clinical course and inferior outcomes as compared to uninfected counterparts. However, these studies included small numbers of patients, and often lacked appropriate comparison groups. We aim to compare clinical characteristics and outcomes of HIV+ and uninfected subjects with MM, with the hypothesis that significant differences will be detected between the two groups.

Methods:

We analyzed all patients with histologically proven MM in the Veterans Aging Cohort Study (VACS). VACS is a prospective, observational cohort, beginning in 1996, of > 40,000 HIV+ and > 80,000 age-, race/ethnicity-, sex-, and clinical site- matched (1:2) uninfected patients under care in the Veterans Health Administration. Clinical variable were obtained via chart review. The variables studied included stage at diagnosis (Durie-Salmon and International Staging System- ISS), bone marrow plasma cell involvement at diagnosis, presence of asymptomatic vs clinical MM, involvement with bone lesions at diagnosis, and presence of extramedullary (EM) involvement during the course of disease. Differences between the HIV+ and uninfected patients were compared using appropriate bivariate methods (chi-squared or Fisher's test, where applicable). All p values were two sided and the level of significance chosen was 0.05.

Results:

A total of 162 patients (62 HIV+, 100 uninfected) with MM were included in this study. Patients were predominantly male 99.4%; 57% were black, 28% white, 15% Hispanic or other ethnicity. Average age at the time of diagnosis was 59, and did not differ between the two groups. The distribution by Durie-Salmon stage was as follows: 28% stage 1, 18% stage 2 and 54% stage 3. By ISS, 43% had stage 1, 25% had stage 2 and 31% had stage 3 disease. 10% had asymptomatic disease. 54% had lytic lesions on skeletal survey. When HIV+ and uninfected patients were compared, based on the available data, there were no statistically significant differences in the distribution of MM by stage, presence of clinically symptomatic MM or presence of lytic lesions. However, we observed a significantly higher rate of the presence of extramedullary disease in the HIV+ as compared with uninfected group (>1 EM site 21% vs 19%, 1 EM site 21% vs 11%, none 57% vs 78%; p value 0.02). Comparison of overall survival between the two groups, and analysis of the impact of HAART on survival are ongoing.

Conclusion:

This is the largest published study to date to compare the clinical characteristics and outcomes of MM between HIV+ and uninfected individuals. We observed a significantly higher rate of EM disease in the HIV+ group, an important finding since EM disease is associated with poor prognosis. Ongoing analysis will provide additional data on treatment responses, including the role of HAART, and a comparison of clinical outcome data between these two groups.