Multiple myeloma at Chris Hani Baragwanath hospital

Background and aims Worldwide, multiple myeloma accounts for 0.8% of all cancers diagnosed, with a variable incidence (Alexander, 2007). In South Africa, in 2009, amongst haematological malignancies, multiple myeloma was the fourth most common in males and the third most common in females (Cancer in South Africa, 2009 National Cancer Registry). Yet, there is a paucity of data regarding multiple myeloma in South Africa with few descriptive studies and case reports (Blattner, et al., 1979; du Preez and Branca, 1991; Patel, 2000; Feller, et al., 2009; Webb, et al., 2013). South Africa has a very high prevalence of human immunodeficiency virus (HIV) infection. In 2010, it was estimated that 5.24 million people in South Africa were HIV-seropositive, with a prevalence rate in the population of 10.5% (Statistics South Africa, 2010). Studies have shown that in HIV-seropositive patients, multiple myeloma occurs at an increased rate, at a younger age and with atypical features e.g. extramedullary plasmacytomas in unusual sites (Cheung, et al., 2005; Grulich, et al., 2007). However, in South Africa, no association between HIV infection and multiple myeloma has been shown (Sitas, et al., 2000; Stein, et al., 2008). This study describes the demographic, clinical, laboratory and radiological findings of patients presenting with multiple myeloma at a large tertiary hospital in South Africa. In addition it describes the therapy, response to therapy, and survival of these patients. Furthermore, it also describes and compares multiple myeloma in HIV-seropositive and HIV-seronegative patients. Patients and methods This retrospective analysis included patients diagnosed with multiple myeloma from 1 January 1998 – 31 December 2010 (13 years). With respect to outcomes the study was concluded on 31 December 2011. Data was processed in Microsoft Excel 2010. Demographic, clinical, laboratory and radiological findings at presentation were documented. Therapy and responses to therapy were noted. Outcomes for the different first-line treatments were contrasted: ANOVA analysis was used to compare progression free survival and Kaplan-Meier survival curves were used to compare overall survival. HIV-seropositive patients were compared with HIV-seronegative patients at presentation: The Welch corrected unpaired t-test was used for continuous data and the Fisher exact test was used for categorical data. Kaplan-Meier survival curves with Chi2 analysis compared overall survival between HIV-seropositive and HIV-seronegative patients. Results A total of 289 patients were included in this study, with 145 males and 144 females (male:female ratio 1:1). The median age at presentation was 58.0 years (range 26 – 86 years) and the peak frequency was in the 50 – 59 year age group i.e. the 6th decade (36.2%). The most frequent clinical features were bone pain (87.4%), constitutional symptoms (77.1%) and symptomatic anaemia (68.9%). Laboratory findings showed anaemia in 91.6% (median haemoglobin 8.8 g/dL), hypercalcaemia >2.75 mmol/L in 35.1% and creatinine >177 μmol/L in 32.0%. The IgG isotype was in seen in 55.0%, the IgA isotype in 19.0%, light chain disease was present in 19.0%, non-secretory multiple myeloma in 2.4% and the subtype was not characterized in 4.5%. No cases of IgM, IgD or IgE multiple myeloma were recorded. Plasma cell leukaemia was noted in 2.8%. Monoclonal protein was detected in the serum in 93.1% (median 36.7 g/L) and in the urine in 87.6% (median 0.36 g/L). Immuneparesis was common and occurred in 87.9%. The median plasmacytosis in the bone marrow (corrected to assess only adequate smears) was 34.0%. Skeletal survey by radiograph showed lytic lesions in 79.2%, vertebral compression fractures in 43.1%, pathological fractures of the long bones in 14.2% and other fractures (e.g. pathological fractures of the pelvic bones) in 8.6%. The majority of patients presented with stage III disease (75.4%; using the Durie-Salmon criteria and 57%; using the International Staging System). Median overall survival for the 289 patients was 15.9 months. A high proportion of patients died within 3 months of presentation (47.3%) and significantly, 41.9% of patients were lost to follow-up. With respect to first-line therapy progression free survival was significantly longer (p = <0.0001) for high dose chemotherapy followed by autologous stem cell transplant prior to any relapse (early ASCT) versus melphalan-prednisone (MP), as well as for early ASCT versus cyclophosphamide-vincristine-doxorubicin-high-dose dexamethasone (CVAD) alone. Kaplan-Meier survival curves showed a significant difference between the different first-line therapy groups (p = <0.0044), and the best survival curve was seen in the early ASCT group. At presentation 6.2% were HIV-seropositive, with a median CD4 count of 313 cells/mm3 and a median viral load of 19304 copies/mL. Significant findings in HIV-seropositive patients were a younger mean age (i.e. 44.7 years), a greater frequency of clinically evident plasmacytoma and a lesser frequency of immuneparesis. There was no difference in the Kaplan-Meier survival curves of HIV-seropositive and HIV-seronegative patients (Chi2 test of the curves p = 0.9073). Conclusions The peak frequency of patients diagnosed with multiple myeloma was in the 50 – 59 year age group (36.2%) and the number of males to females was nearly equivalent. The majority of patients presented with an advanced stage of disease (Salmon-Durie stage III or International Staging System stage III) and many died within 3 months of initial presentation. Recipients of early ASCT had a significantly better progression free survival and overall survival as compared to other first-line therapies. HIV-seropositive patients with multiple myeloma presented at a younger age with a higher rate of plasmacytoma and a lower frequency of immuneparesis. There was no difference in overall survival in HIV-seropositive versus HIV-seronegative patients. To the best of our knowledge, this is the largest descriptive study of multiple myeloma in sub-Saharan Africa. Moreover, this is also the largest descriptive study of patients in sub-Saharan Africa who were HIV-seropositive at the time of presenting with multiple myeloma.
Submitted for the degree of Master of Medicine (in the specialty of Internal Medicine) to the University of the Witwatersrand