The Current Situation of Multiple Myeloma Treatment in Japan: A Cross-Sectional Analysis Based on Health Insurance Claims Data
Authors: Uno Shuji , Saito Kazushige , Janune Danilo , Iwasaki Kosuke , Ohtsu Tomoko 
Published: October 2019

Abstract
Introduction: Multiple myeloma (MM) is a rare disease with an estimated annual prevalence of 5.3 per 100,000 persons in Japan (Center for Cancer Control and Information Services, 2017). The median age of Japanese patients at the time of diagnosis is 66 years (Japanese Society of Myeloma, 2016). Bortezomib, thalidomide, lenalidomide, pomalidomide, panobinostat, carfilzomib, elotuzumab, ixazomib, and daratumumab have been approved for MM treatment in Japan. Despite a systematic review on treatment costs for relapsed/refractory MM patients in Japan (Yamabe et al. 2015) and a study identifying factors influencing drug choice for first-line treatment of MM (Bolt et al., 2018), comprehensive data on the current situation with MM treatment costs in Japan are lacking. We analyzed health insurance claims data to demonstrate the current status of MM treatment patterns and associated costs in Japan.
Methods: We used a health insurance claims database containing records of 19.8 million individuals from 314 acute care hospitals. Diagnostic information was based on the 10th revision of the International Classification of Diseases (ICD10). Drugs were coded based on the Anatomical Therapeutic Chemical Classification System. The monthly medical cost per patient (MMCP) was analyzed from April 2008 to December 2016 as follows: total MMCP, MMCP for MM drugs, and MMCP for other costs (hospitalization, surgery and tests, etc.). The share of each agent in the medical cost of MM drugs was also analyzed throughout the same period. We selected patients with ≥ 1 diagnosis of MM (ICD10 code C90.0). The observation period for each patient started at the latter date of first medical care day for any disease or the first MM diagnosis and ended at the last medical care day for any disease.
Results: We identified 19,137 MM patients. Total MMCP showed an increasing trend until lenalidomide was launched in Japan in 2010, at which point MMCP began to stabilize (Figure 1). MMCP per MM drug showed an increasing trend during the entire study period, but other medical costs showed a decreasing trend after the launch of lenalidomide (Figure 2). Detailed analysis of other costs showed that oral medication cost ratio increased just after the launch of lenalidomide and further increased gradually from 2015, while the basic hospitalization cost ratio gradually decreased after the launch of lenalidomide (Figure 3). Analysis of the contribution of each drug to the medical cost of MM drugs showed that the lenalidomide cost reached almost 40% of the share immediately after its launch and remained stable thereafter (Figure 4). Lenalidomide maintained its stable share even after the launch of newer drugs (eg, pomalidomide and carfilzomib) (Figure 4).
Discussion: Although a significantly better prognosis has been reported in MM patients treated after 2010 (Shibayama et al. 2013), our data show that lenalidomide addition to MM treatment in Japan did not increase total MMCP for approximately 5 years following lenalidomide launch. This may be due to the prescription of lenalidomide leading to improved MM management in clinical practice, as indicated by changes in the medical cost share of each drug. Such interpretation is also corroborated by a decrease in injection cost and an increase in oral medication cost. It can be argued that as lenalidomide is orally administered, hospitalization and the use of other materials are reduced, resulting in treatment cost reduction. The hospitalization costs for patients receiving lenalidomide maintenance therapy were lower than those for patients not receiving any maintenance therapy (Ashcroft et al. 2018). The Guidelines for the Treatment of Multiple Myeloma (Japanese Society of Myeloma, 2016) present the regimen lenalidomide + low-dose dexamethasone (Rd) for newly diagnosed MM patients and the induction regimen Rd + bortezomib (RVd) for transplant-eligible MM patients as a grade A treatment recommendation and specify a lenalidomide-based triplet regimen as a salvage treatment option for relapsed and/or refractory MM patients. Such a recommendation may explain the relatively stable share of lenalidomide medical care costs despite the launch of new drugs (pomalidomide and carfilzomib) in Japan.

Disclosures
Uno: Celgene K.K.: Employment. Saito:Celgene K.K.: Employment. Janune:Milliman: Employment. Iwasaki:Milliman: Employment. Ohtsu:Celgene K.K.: Employment.