Abstract
Introduction: The incidence and prevalence of multiple myeloma (MM) is increasing in Asian countries. In Taiwan, increased MM incidence between 2007–2015 was accompanied by a decrease in fatality and increased median survival, coinciding with the reimbursement of several novel agents under the National Health Insurance. Since then, treatment for MM has continued to evolve, most notably with availability of anti-CD38 monoclonal antibodies such as daratumumab (D). We investigated temporal trends in MM treatment patterns and clinical outcomes from 2013 to 2022, a period encompassing onset of reimbursement for lenalidomide (R) in first line (1L) in patients with transplant-ineligible (TI) MM from February 2020, and D for second line (2L) and beyond from April 2020.
Methods: This population-based study used the Taiwan National Healthcare Insurance Research database (NHIRD) and the linked Registry of Catastrophic Illness (RCI). All adult patients with newly diagnosed (ND) TI MM (ICD-10 codes C90.0 or C90.0x) in the RCI from 2013 to 2022 were enrolled. Patients with other pre-existing primary cancers were excluded. Eligible patients who had received MM treatment were followed up until death, or end of the observation period (December 31, 2023), whichever occurred first. Overall survival (OS) was estimated using Kaplan-Meier methods. Hazard ratios (HR) were obtained from multivariate Cox regression model adjusted for age, gender, comorbidities and time-period.
Results: The analysis included 2151 patients with NDMM between 2013–2017 and 2643 between 2018–2022. Patient demographic characteristics were similar in both periods. Between study periods, VTd use in 1L (approximately 50% of patients) was unchanged, use of V(bortezomib)R-dexamethasone(d) increased from 0-17.59%, and use of regimens containing melphalan and alkylators decreased. In 2L D-containing regimens increased from 2.23% to 20.40%, VRd from 1.89% to 13.04%, whereas use of Rd and alkylators decreased. Similar trends were observed in third line (3L).
Between 2013 and 2017, 105 of 2151 patients (4.88%) remained on 1L therapy and 832 (38.68%) died before receiving 2L. Among 1214 (56.44%) who received 2L treatment, 73 patients (6.01%) remained on 2L, and 375 (30.89%) died before initiating 3L. In the 2018–2022 period, 527 of 2643 patients (19.94%) remained on 1L therapy and 851 (32.20%) died before receiving 2L. Among 1265 (47.86%) who received 2L, 281 patients (22.21%) remained on 2L, while 275 (21.74%) died prior to starting 3L.
OS was evaluated between 2013–2017, and between 2018–2020 and 2021–2022 to assess the impact of the inclusion of reimbursement for R for NDMM and D for relapsed refractory MM in 2020. There was a statistically significant improvement in OS over time. Median OS (95% CI) was 2.17 years from 2013–2017, 2.32 years 2018–2020 and was not reached in patient diagnosed between 2021–2022. The HR for death compared to the 2013–2017 period was 0.907 (95% CI 0.837–0.984; p=0.0185) for 2018–2020 and 0.734 (0.659–0.817; p<0.0001) for 2021–2022.
Conclusion: The NHIRD provides health insurance for the whole population of Taiwan, allowing complete and longitudinal data collection across all treatment settings. We observed increased uptake of novel agents after their reimbursement under the National Health Insurance that coincided with a decrease in attrition rates and an increase in OS. Reduced attrition between 1L and 2L, between 2L and 3L, a higher percentage of patients who remained on treatment, and longer OS in the 2018–2022 period could reflect increased use of the VRd regimen and D-containing regimens during these years versus the 2013–2017 period. The use of novel therapies appears to be contributing to improved OS in patients with MM in Taiwan. Earlier access to more effective new treatments could provide further benefits for patients.
