Abstract
A recent prospective cancer screening trial including over 77,000 individuals followed-up for over 10 years shows that multiple myeloma (MM) is consistently preceded by a precursor state, monoclonal gammopathy of undetermined significance (MGUS). Clinically, most newly diagnosed MM patients are unaware of their prior MGUS state. Importantly, among individuals diagnosed with MGUS, only a small proportion will develop MM or a related malignancy during their lifespan. Current clinical guidelines suggest lifelong, annual monitoring of individuals diagnosed with MGUSto detect progression to MM or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop MM is unknown. In addition, as MGUS is usually diagnosed during work-up for another disorder, the impact of comorbidity in MM patients with prior knowledge of MGUS is unknown. We assessed the impact of prior knowledge of MGUS in relation to MM survival.
The study cohort consisted of 14,798 individuals diagnosed with MM in Sweden 1976-2005, with follow-up until 2007. A total of 394 patients had previously been diagnosed with MGUS. Patients diagnosed with MM were identified through the Swedish Cancer Register. MM patients with prior knowledge of MGUS were identified from a nationwide MGUS cohort which was established from in and out-patient units from major hospital-based hematology/oncology centers in Sweden. Details of sex, date of birth, date of diagnosis, type and concentration of M-protein at MGUS diagnosis, and comorbidities (autoimmune diseases, infections, other malignant diseases, ischemic heart diseases, heart failure, cerebrovascular diseases, chronic lung diseases and renal diseases) were gathered for all patients. Survival rate from time of MM diagnosis comparing patients with and without prior knowledge of MGUS was calculated with a Kaplan Meier method. Risk factors for death were analysed in a Cox proportional hazards model where relative risks (RR) and 95% confidence intervals (CIs) were calculated. A Chi-square test was used to evaluate whether there was a significant difference in comorbidities.
MM patients with prior knowledge of MGUS had significantly (RR = 0.86; CI = 0.77-0.96) better survival (median = 2.8 years; 95% CI = 2.6-3.3) than MM patients without prior knowledge of MGUS (median = 2.1 years; 95% CI = 2.1-2.2; Figure). Older age at diagnosis (RR = 1.04; 95% CI = 1.04-1.05) was associated with an inferior survival, whereas female sex and recent year at diagnosis were related to improved survival: RR = 0.86 (CI = 0.83-0.89) and 0.95 (CI = 0.95-0.95), respectively. There was no difference in survival comparing MGUS patients with high (>1.5 g/dL) versus low (<1.5 g/dL) M-protein concentration (RR = 1.01; 95% CI 0.72-1.41). Unexpectedly, M-protein concentration ≤0.5 g/dL at MGUS diagnosis was associated with poored survival than M-protein concentration greater than 0.5 g/dL (RR = 1.86; 95% CI = 1.13-3.04, p=0.014).
Autoimmune diseases (p<0.001), infections (p<0.001), other malignant diseases (p<0.001), ischemic heart diseases (p<0.001), heart failure (p<0.001), cerebrovascular diseases (p<0.001), and renal diseases (p<0.001) at diagnosis of MM were significantly more common in MM patients with prior knowledge of MGUS than in MM patients without.
Based almost 15,000 MM patients diagnosed in Sweden between 1976 and 2005, for the first time, we found that prior knowledge of MGUS is associated with better survival (median overall survival 2.8 versus 2.1 years). Given patterns of co-morbidities, the observed survival difference is likely a reflection of the fact that MGUS patients are evaluated more often for signs of MM progression and may be diagnosed/treated at an earlier stage. The finding that low-risk MGUS patients that develop MM had a shorter survival rate is interesting and may be due to less intense monitoring and needs to be studied further. Our observations raise the question whether screening for MGUS, e.g., above the age of 50, could translate into earlier detection/treatment of MM (“early myeloma“) and lead to better survival. Future prospective studies are needed to explore these findings further.
Turesson:Celgene Corp: Honoraria.
