Introduction
The treatment (tmt) for multiple myeloma (MM) is evolving with the introduction of novel immunomodulatory drugs (IMiD), monoclonal antibodies (MoAB), and proteasome inhibitors (PI). As new efficacious therapies are approved, the prevalence of MM continues to increase and remains an incurable disease. There is limited real-world evidence describing these temporal changes (Song 2016, Curr Med Res Opin; Fonseca 2017, Leukemia). This study characterizes trends in MM tmts and patient (pt) survival from 2011-19 in the US-based Flatiron electronic health records (EHR) database.
Methods
Data analyzed were from an enhanced database of oncology EHR contained in the Oncology Services Comprehensive Electronic Records (OSCER), generated by Flatiron Health that includes additional unstructured data processing (New York, NY, March 31, 2019). OSCER represents a longitudinal, demographically and geographically diverse database with data from over 265 cancer clinics representing over 2 million active pts treated at primarily community-based hematology/oncology practices in the US. Inclusion criteria included adult pts ≥18 years (yrs) with a diagnosis of MM (ICD9: 203.x; ICD-10: C90.x) and at least two clinic visits after 2011. Pt and disease characteristics were characterized; line of therapy (LOT) (1-5), year of therapy initiation, and all tmt regimens received. Follow-up time was measured from tmt index until death or last follow-up. Kaplan-Meier overall survival (OS) proportions were estimated from LOT tmt index.
Results
A total of 9289 pts were identified. At diagnosis the median age was 69 yrs, with 54% of pts male and 68% white. The majority of pts were treated in the community setting (89%) and 11.5% presented with high risk cytogenetics (del17p, t(4;14), t(14;16)). International Staging System (ISS) data was available in 49.2% of subjects, with 16.6%, 16.1% and 16.3% stage 1, 2, and 3 respectively.
Among the 91% of pts who received tmt for newly diagnosed MM, median time to tmt was 30 days. In 2017-18, triplet combination (comb) PI-IMiD-dexamethasone (dex) was the most common front (48%) and second line regimen (27%); and the use of this comb increased in both first and second lines over the study period. In contrast, the use of IMiD or PI -dex doublet regimens decreased. In third line setting, PI-IMiD-dex remained the most common comb in 2017-18 (21%) but gradually decreased over the study period with a dip in 2013-14 while MoAB-IMiD-dex combs increased from 3% to 12% (2015/16-2017/18). In second, third, and fourth line MoAB-IMiD-dex comb increased to 8%, 12%, and 14% respectively beginning in 2015 (Table 1). MM tmt regimens changed over the study period, most notably in the first and second LOTs. By 2017-18, triplets replaced doublets as the most common front line (58%) and second line (45%) therapies over the study period. Across all LOTs, triplets were the most prescribed comb in 2017-18 with 42%, 42% and 30% in third, fourth, and fifth lines. Over the study period, monotherapies decreased to 12% in frontline, but their use has remained constant in later lines (Table 2). Overall, 26% of pts received a transplant during follow-up.
Approximately 34% of pts survived until the end of follow-up. With each LOT, OS deceased. Median OS of pts treated in first line was 57 months and decreased to 44 months, 32 months, and 25 months in second, third, and fourth lines respectively (Figure 1). OS of MM pts who received first line tmt appears to increase the more recently they were diagnosed. Median OS of MM pts diagnosed in 2013-14 was slightly longer compared to pts diagnosed in earlier yrs (2011-12); 60 months compared to 56 months. Median OS was not reached in 2015-16 (Figure 2).
Conclusion
Triplet therapies have replaced doublet therapies over time as more options became available to MM pts, especially in frontline setting; frontline monotherapies have nearly halved since the beginning of the study period. In 2015, tmt patterns begin to shift as MoAB based triplets were approved and comprised a higher proportion of the regimens in the relapsed and refractory population. Yet, the majority of pts are still receiving PI-IMiD-dex triplets. OS estimates suggest survival in front line treated pts is slowly increasing in recent yrs. These data illustrate the current tmt landscape of MM and the changes that have occurred since the introduction of novel therapies over the past 8 yrs. MM disease management continues to evolve.
Braunlin:Amgen, Inc.: Employment. Belani:Amgen, Inc: Employment, Equity Ownership. Buchanan:Amgen Inc.: Employment, Other: Owns Amgen stock, Research Funding. Kim:Amgen, Inc.: Employment, Equity Ownership.
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