Economic Evaluations of Targeted Therapy and Risk-Stratified Treatment Approaches in Multiple Myeloma

Abstract

Multiple myeloma (MM) is a malignant plasma cell disorder accounting for 1% of all cancer diagnoses worldwide and 13% of all hematologic malignancies [1]. Worldwide, the incidence of MM is 0.4 to 5 per 100,000 people per year [2]. Incidence rates are higher among males than females, people of African descent, and increase rapidly until age 84 and then decline. In the Netherlands, the annual incidence rate is 5 per 100,000 with a median age of 70 at diagnosis [3]. The clinical characteristics of MM vary from asymptomatic patients to those with malignant disease. Nonetheless, the disease has a very characteristic presentation such as lytic bone disease, renal insufficiency, anemia, hypercalcemia, the presence of M-proteins found in the serum and/or urine and immunodeficiency [4]. Disorders of the central and peripheral nervous system are also common [5]. The development of hemorrhagic diathesis or thrombosis is also a risk for MM patients with bleeding present in 15-30% of patients and a 3% risk of thrombosis [6]. MM is considered a severe disease in terms of quality-of-life impact and life expectancy and remains incurable. The survival of multiple myeloma patients has improved substantially in the past decade and is attributable to the introduction of novel (‘targeted’) therapies bortezomib (Velcade®), thalidomide (Thalidomid®), and lenalidomide (Revlimid ®), as well as improvements in the use of autologous stem cell transplantation and supportive therapy [7, 8]. Newly diagnosed patients can now expect to live an average of 5-7 years, with some patients living longer than 10 years [9, 10]. In fact, many patients are dying with and not necessarily due to the underlying disease. Prognosis has shown to be associated with treatment but an independent relationship exists with a number of clinical factors and markers for tumor burden and biology. The first staging system to predict prognosis for MM patients was devised 25 years ago by Durie and Salmon (DS) and is based on measurement of hemoglobin, paraprotein concentration and renal and bone disease [11]. Due to advances in treatment that produce complete remissions (CR) and the complexity of the application of the DS staging system, a new International Staging System (ISS) was developed. By applying regression techniques on data from 17 institutions worldwide collected for 11,171 patients [12], the ISS is based on two known markers of disease activity in MM, albumin and β2-microglobulin, which were found to be significant predictors of survival. The ISS divides patients into 3 distinct prognostic groups on the basis of these two markers, which can be evaluated at virtually any clinical laboratory (Table 1). It is important to note that the DS and ISS staging system were studied in patients treated prior to the advent of new active agents. Thus, additional studies validating such prognostic factors are necessary in the present era of novel therapy.