Abstract
Introduction Improvement in disease treatment including access to novel agents such as anti-CD38 monoclonal antibodies has significantly improved survival outcomes in patients with transplant-ineligible multiple myeloma (TIE MM). However, reimbursement timelines of novel agents and criteria vary across countries. In Japan, novel treatments are reimbursed in accordance with the label shortly after regulatory approval. For example, use of daratumumab based therapy in the TIE-MM frontline setting has been reimbursed since August 2019. While in Taiwan, reimbursed frontline therapy in the 1L TIE setting is limited to immunomodulatory imide and proteasome inhibitor-based therapy. Daratumumab use in the relapsed and refractory setting was approved in 2017 and reimbursed in 2020, with coverage limited to 22 infusions. This study uses a matching-adjusted indirect comparison (MAIC) to evaluate the differences in overall survival (OS) of TIE-MM patients in Japan and Taiwan.
Methods We conducted an unanchored Bayesian and Frequentist MAIC using definitive, nationally representative retrospective real-world data. In Japan, de-identified patient-level data were sourced from the Medical Data Vision (MDV) DPC database, which includes over 30 million patients across >519 (29.1%) acute-care hospitals and has been widely used in oncology outcomes research.As of August 2024 it covers approximately 9.9% of the Japanese population. In Taiwan, summary-level data were derived from the National Health Insurance Research Database, a comprehensive claims database covering >99% of the population. The study population included patients diagnosed with TIE-MM between Jan 1 and Dec 31, 2020, received 1L MM therapy, were ≥20 years old, and had ≥12 months of baseline data. Patients receiving autologous stem cell transplantation, having prior MM treatment, or other primary cancers were excluded. Patients follow up data was captured until death or date of cut off (Dec 31, 2023). The primary outcome was OS defined as time from treatment initiation to death from any cause. Clinically relevant baseline characteristics, including age, sex, and Charlson Comorbidity Index (CCI) validated by haematologists, from the Taiwan cohort (N=446) were used as covariates to reweight the Japan MDV cohort (N=244). All analyses were performed in accordance with the National Institute for Health and Care Excellence Guide to the Methods of Technology Appraisal (TSD18: Methods for population-adjusted indirect comparison).
Results Prior to MAIC weighting, Japanese patients were older (mean age: 74.2 vs. 71.2 years) with slightly more male patients (51.5% vs 51.3%) and had higher comorbidity burden (mean CCI: 5.36 vs. 3.12) than Taiwanese patients. After reweighting, the Japan cohort were matched successfully with the Taiwanese cohort in age (71.2), gender (51.3%) and CCI (3.23) with the effective sample size of 244. In the unadjusted analysis, the Bayesian and Frequentist estimates of the unadjusted hazard ratios (HR) were 0.3391 and 0.339 (95% credible interval [CrI]: 0.265–0.429, 95% confidence interval [CI]: 0.267-0.43). After MAIC adjustment, Japanese patients continued to demonstrate an overall survival advantage, with a HR of 0.2403 and 0.24 (95% CrI: 0.173–0.326, 95% CI: 0.177-0.327). The median survival time for Japan population was not reached at 4 years but was approximately 27 months for Taiwan. The Frequentist restricted mean survival difference was 14.6 months (95% CI: 11.9–17.3), suggesting that Japanese patients first-line lived over a year longer than Taiwanese patients over the 4 years of follow up.
Conclusion In this real-world comparative study of TIE-MM patient survival outcomes in Japan and Taiwan, Japanese patients were found to have a significantly longer overall survival. This survival advantage was present prior to MAIC adjustment despite Japanese patients being on average older and having a higher comorbidity burden and continued to be evident following adjustment. Despite limitations of this analysis in terms of potential unmeasured confounders, for example disease specific characteristics such as stage at diagnosis, and differences in clinical practice, the observed difference in unadjusted and adjusted survival outcomes between Japanese and Taiwanese patients may be partially explained by differential access to innovative therapies.
