Patterns of Medication Use in Patients with Relapsed and/or Refractory Multiple Myeloma
Authors: Hagiwara May , Moynahan Aaron , Cong Ze , Chen Yaozhu J. , Duchesneau Emilie , Hurley Dana , Delea Thomas E. 
Published: October 2019

Abstract
Background
For patients with multiple myeloma (MM) who are refractory to or relapsed after initial therapy, current US clinical guidelines recommend treatment with proteasome inhibitors (PIs) (e.g., bortezomib [V] or carfilzomib [K]) and/or immunomodulatory drugs (IMiDs) (e.g., lenalidomide [R], thalidomide [T] or pomalidomide [P]), combined with corticosteroids. Data on the real world use of these medications, such as rate of initiation of a new line of therapy (LOT), treatment regimens within LOTs, and duration of treatment (DOT), among US patients with relapsed and/or refractory MM are limited.
Methods
This was a retrospective cohort study of medication use patterns among US patients with MM who were refractory to or relapsed after initial therapy. Data were from the MarketScan commercial and Medicare research databases between Jan 2006 and Dec 2013 (study period). Study patients included adults who were diagnosed with MM (ICD-9-CM code 203.0x) and initiated second line (2L) therapy during the study period, and were continuously enrolled from ≥180 days prior to MM diagnosis to ≥30 days after initiation of 2L. LOT was identified using claims for PIs, IMiDs, and other MM treatments; corticosteroids were not used in identification of LOTs. Treatment regimens were defined based on claims for MM therapies during the first 90 days after start of a LOT. The start date of a new LOT (and the end date of the current LOT) was identified based on the date of the first claim for a new MM therapy (i.e., not in the current regimen), a claim for any MM therapy after a gap of >90 days without a claim for any MM therapy, or end of follow-up (EOF), whichever occurred first. Time within LOT was separated into on- and off-therapy periods; on-therapy period ended on the date of the last claim during the LOT for any therapy in the regimen (or for the last LOT, EOF if the last claim during the LOT was <90 days from EOF). The distribution of MM patients by treatment regimen was assessed by LOT (2L, third line [3L], and fourth or subsequent line [4L+]) and by date of LOT initiation (Jan 2006 - May 2008, Jun 2008 - Jun 2012, and Jul 2012 - Dec 2013). Kaplan-Meier estimates of DOT were calculated for each regimen by LOT (2L and third or subsequent line [3L+]). Patients were censored if last claim for MM therapy was <90 days from EOF. For reporting purposes, regimens were classified into 6 mutually-exclusive categories: K-based regimens (any K), P-based regimens (P, no K), R-based regimens (R, no K or P), V-based regimens (V, no K, P, or R), T-based regimens (T, no K, P, R or V), and other regimens (other MM medication, no K, P, R, V, or T). An additional analysis based on all prevalent MM patients with 1+ day of enrollment in 2013 was conducted to estimate the rate of MM therapy new starts by LOT and patient's age/sex.
Results
A total of 4,693 patients were included in the study, representing 7,683 LOTs (2L=4,693, 3L=1,868, and 4L+=1,122); 56% were male, 59% were in commercial plans, and 20% had transplant before 2L. Mean (SD) age at 2L initiation was 64 (12) years. Use of R-based regimens was greatest in 3L. Based on the regimen classification described above, use of V-based regimens was similar across LOTs (Figure 1A); P- and K-based regimens were used infrequently (<2% of all LOTs) and predominantly in 3L and 4L+. Over time, use of T-based regimens and regimens without PIs or IMiDs decreased in all LOTs while use of R- or V-based regimens increased in all LOTs (Figures 1B-1D). Median DOT (in days) was similar in 2L and 3L+ and was longer for R-based regimens (2L: 277 days; 3L+: 282 days) vs. other regimens (2L: 121-180 days; 3L+: 155-171 days) (Figure 2). Among 3,329 prevalent MM patients identified in the additional analysis, the rate of new starts per 100 person-years was 17.7 for 1L, 8.1 for 2L, 3.7 for 3L, and 2.7 for 4L+ (Table 1).
Conclusions
Among relapsed or refractory MM patients in the US, use of R- and V-based regimens increased since 2008, while the use of T-based regimens declined. The portion of patients receiving K- and P-based regimens was small but increasing. Median duration of therapy of R-based regimens was about 100 days longer than that of other regimens. These data could be useful for economic evaluations and research and budget planning.
Table 1. Rate of New Starts on MM Therapy per 100 Person Years (PSY) Sex, Age PSY 1L 2L 3L 4L+ Female, <65 2,527 18.1 8.4 4.2 3.0 Female, ≥65 2,412 15.1 6.2 3.0 2.3 Male, <65 2,818 21.4 10.5 4.6 3.2 Male, ≥65 3,034 16.0 7.1 2.8 2.3 Total 10,791 17.7 8.1 3.7 2.7

Disclosures
Hagiwara: Onyx Pharmaceuticals: Research Funding. Moynahan:Onyx Pharmaceuticals: Research Funding. Cong:Onyx Pharmaceuticals: Employment, Equity Ownership. Chen:Onyx Pharmaceuticals: Employment. Duchesneau:Onyx Pharmaceuticals: Research Funding. Hurley:Onyx Pharmaceuticals: Consultancy. Delea:Onyx Pharmaceuticals: Research Funding.