Burden of Disease Progression in Patients with Multiple Myeloma Who Have Received at Least One Line of Therapy in the US
Authors: Hagiwara May , Delea Thomas , Panjabi Sumeet , Yucel Emre , Fonseca Rafael 
Published: October 2019

Abstract
Introduction
Previous studies have documented substantial economic burden for multiple myeloma (MM) patients (pts). However, data on the economic burden of disease progression in the US are limited. In this study, we estimated effects of disease progression on healthcare resource utilization (HRU) and costs among pts with MM who have received at least one line of therapy (LOT) in the US.
Methods
Data from the Truven Analytics MedStat MarketScan® Commercial Claims and Encounters and Medicare and Coordination of Benefits databases were used. A retrospective incident user cohort of adult pts with a confirmed diagnosis (Dx), defined as ≥1 inpatient or ≥2 non-diagnostic outpatient claims 30-365 days apart with diagnosis, of MM who initiated a course of MM therapy during the study period (Jan 1, 2006 to Dec 31, 2016) was identified. The first date with Dx for MM was defined as the "Dx date" and LOT was identified based on a published algorithm. Pts were excluded if they had a gap in enrollment during the period beginning 6-month before the Dx date through 30-days after the first LOT (1L) initiation date, received MM therapy or unclassified antineoplastic medications before the Dx date or stem cell transplant (SCT) at any time during the study period, or had missing information required to identify LOT or assess baseline characteristics or study outcomes. The 12 months after initiation of each LOT was designated the "event identification period" for progression. Disease progression was defined as advancement to the next LOT, ICD-9/10 or CPT/HCPCS diagnosis or procedure codes indicative of bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal related events, or acute kidney disease while off MM therapy, or death. The "event date" for progression was defined as date with evidence of progression. For each pt with progression, one pt without progression was randomly selected and assigned an index date to ensure that distribution of time from LOT initiation to event date for pts with progression was the same as that for pts without progression. For each LOT (L1-L4), annual HRU and costs from index date through disenrollment or the end of the study period were compared for pts with vs without progression using inverse probability of treatment weighting (IPTW) to adjust for differences between groups in baseline characteristics including year of index date, age, gender, region, plan type, Medicare status, comorbidities, and pre-index HRU and healthcare costs. All costs were adjusted to 2016 US dollars. In a subgroup analysis, HRU and costs were evaluated for LOTs initiated from 2013 to 2016 to reflect patterns of treatment in current era.
Results
Of the 28,184 adult MM pts who received one or more MM therapy during the study period, 11,179 qualified for the study, including 4468 and 6598 pts with and without progression during 1L, respectively. The corresponding numbers for 2L, 3L, and 4L were 1563 and 2207, 618 and 714, and 244 and 260, respectively. Mean age at index date was 68 years; 57% were male. After IPTW, all baseline characteristics were well balanced in all LOTs with standardized mean differences <0.1 for all characteristics. The mean number of hospitalizations per year was greater for patents with progression in all LOTs, with differences ranging from 0.46 (95%CI 0.40, 0.52) for 1L to 0.89 (95%CI 0.67, 1.11) for 3L. In all LOTs, annual costs of inpatient and outpatient services were greater for pts with progression while costs of outpatient prescriptions were greater among patient without progression. Total healthcare costs were greater for pts with vs without progression in all LOTs with hospitalizations and outpatient visit costs being key drivers. Total incremental annual costs in those who progressed were higher by $30,381 (1L), $33,064 (2L), $34,495 (3L), and $25,163 (4L). When the analysis was restricted to LOTs initiated between 2013 and 2016, the incremental costs in patients who progressed were greater in the most recent era: $52,739 (1L), $49,012 (2L), $25,329 (3L), and $65,400.
Conclusions
For MM pts receiving drug therapy, the economic burden of disease progression is substantial across all LOTs and this burden is greater in the most recent era (2013 to 2016). Treatments that prevent or delay progression are likely to yield important reductions in downstream disease management costs. These savings should be considered in frameworks assessing the value of innovative treatments for MM.

Disclosures
Hagiwara: Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Amgen: Research Funding; Amgen: Consultancy; Policy Analysis, Inc: Employment. Delea:Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Policy Analysis Inc.: Employment. Panjabi:Amgen: Employment, Equity Ownership. Yucel:Amgen: Employment, Equity Ownership. Fonseca:Mayo Clinic: Employment; Amgen: Consultancy.