Patient Characteristics, Treatment Patterns and Outcomes Among Relapsed/Refractory Multiple Myeloma (RRMM) Patients in Japan
Authors: Jun Gyungjin , Luptakova Katarina , Koizumi Hiroo , Iwasaki Kosuke , Hiroi Shinzo , Soeda Junpei 
Published: November 2019

Abstract
Background
MM is one of the most common hematologic malignancies in Japan and deaths due to MM represent 1.1% of all cancer deaths in 2014. Proteasome inhibitors and immunomodulatory drugs have led to improvements in overall survival (Kumar et al. Blood 2008); a trend that was confirmed in a large retrospective analysis of Japanese patients across the years 2001-2012 (Ozaki, et al, Blood Cancer Journal, 2015). The Japan Society of Hematology guideline for MM and guidelines for diagnosis and management of MM by the Japanese Myeloma Study Group recommend bortezomib (approved 2006), thalidomide (approved 2008) and lenalidomide (approved 2010) along with other anti-MM agents for treatment of RRMM. The objective of this study is to describe patient characteristics, contemporary treatment patterns, and outcomes in patients with RRMM using real world data.
Method
Patients with MM diagnoses based on ICD-10-CM (C900) codes, during the study period of April 2008 to January 2016, were followed using Japanese health insurance claims data provided by Medical Data Vision (MDV) in this retrospective cohort study. Index date was defined as the first observed claim for MM treatment after at least 90 days of washout period from enrollment. Progression to a subsequent line of therapy was defined as switch to another drug combination > 60 days from index date or retreatment following a treatment gap of > 90 days. Time to next treatment (TTNT) was used as a disease progression proxy and was measured as the time from the start date of the line of therapy to the start date of a subsequent line of therapy. Descriptive analyses were carried out to examine patient characteristics, treatment patterns and outcomes. Observations were censored at time of loss to follow up/end of study period.
Results
Among a total of 12,348 patients with a diagnostic code of MM between April 2008 and January 2016, 358 patients who received at least one treatment episode were identified with RRMM. Median follow-up was 34.0 months. Median age was 71.0 years; 34% were aged 65-74 years and 35% were 75 years or older. Male patients constituted 56%, however female patients over 80 years outnumbered male patients. Cytogenetic testing was performed in 70%. Thirteen percent of patients received stem cell transplant and 22% of those were over 65 years. Across the lines of therapy for RRMM, the regimens were: bortezomib (V) ± dexamethasone (d) (V ± d, 27.7%), melphalan (M) + prednisone (P) (MP, 20.9%), lenalidomide (R) ± d (10.9%), VM ± P (4.2%), V-cyclophosphamide (C) ± d (VC ± d, 3.1%), V + other (2%), R + other (0.3%), and others (50.0%). Among patients treated with others, a corticosteroid alone such as dexamethasone or prednisone was commonly used and alkylating agents or thalidomide were also used. Among patients treated with V-based regimen, 75% had at least one medical claim for acyclovir or valacyclovir for prophylaxis against risk of infection. Among patients treated with R-based regimen, 69% had at least one medical claim for aspirin, enoxaparin or warfarin for thromboembolism prophylaxis. Median duration of treatment was 5.1 months for patients with V ± d, 5.2 months for patients with MP and 5. 3 months for patients with R ± d. Median daily dose of R was 13.3 mg. Median TTNT for patients treated with V ± d, MP and R ± d was 11.5 months, 8.4 months and 12.5 months, respectively.
Conclusion
This is the first database analysis based on health insurance claims data of MM in Japan. This analysis of treatment patterns found that doublet regimens were used mainly in Japanese patients with RRMM, with V ± d and MP regimens being the most common. The duration of each regimen was relatively short and the majority of patients discontinued therapy prior to disease progression. Recent evidence has shown triplet regimens have better efficacy than doublet regimens among RRMM patients. Triplet regimens containing novel agents with sustainable efficacy, and a manageable safety and tolerability may increase the likelihood of prolonged therapy which has been correlated with better outcomes over fixed duration therapy in MM. This study may underestimate the duration of each treatment since the data were not censored.

Disclosures
Jun: Takeda Pharmaceutical Company Limited: Employment. Luptakova:Takeda Oncology: Employment. Koizumi:Takeda Pharmaceutical Company Limited: Consultancy. Iwasaki:Takeda Pharmaceutical Company Limited: Consultancy. Hiroi:Takeda Pharmaceutical Company Limited: Employment. Soeda:Takeda Pharmaceutical Company: Employment.