Study Design and Data Source
This was a retrospective US claims-database study that used the IBM® MarketScan® Commercial Claims and Encounters (CCAE) and Medicare Supplemental (MDCR) databases. These databases capture utilization and the associated costs of inpatient and outpatient medical services and pharmacy services, in addition to patient demographics and enrollment status. Only de-identified patient data are contained within the CCAE and MDCR databases and they are both fully compliant with the Health Insurance Portability and Accountability Act (HIPAA).
Adult patients (≥ 18 years of age) diagnosed with MM between 1 January 2012 and 30 June 2021 were selected from the MarketScan CCAE and MDCR databases. MM was identified according to International Classification of Diseases (ICD), Ninth/Tenth Revision Clinical Modification codes (ICD-9: 203.0x; ICD-10: C90.0x). Patients were required to be continuously enrolled in medical/pharmacy benefit plans and not exposed to MM treatments for at least 12 months prior to their first-observed MM diagnosis. Patients diagnosed with other malignancies prior to the first-observed MM diagnosis date were excluded from the study.
At the index date, patients were required to have received at least four prior LOTs, including TCE, defined as having received a PI, IMiD, and anti-CD38 targeted mAb recommended by the NCCN guideline  after their first-observed MM diagnosis. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study. Additionally, the index date was required to have occurred after 1 January 2017 in order to capture contemporary cost estimates. Lastly, patients were required to have had continuous enrollment in a medical/pharmacy benefit plan and to have survived at least 1 year after index date. Patients were followed until the end of the study period, continuous enrollment, or death, whichever occurred first.
Treatment Regimens and LOT Definitions
Treatment regimens and LOT definitions have been described in detail previously . A summary of these methods is provided below. Each treatment regimen was defined by a start and end date and was comprised of ≥ 1 MM medications recommended by the NCCN guidelines . Medical and pharmacy claims were used to identify treatment regimens during the first 60 days after study initiation. The initiation date of the first (i.e., index) treatment regimen was the date of the first claim for an identified MM treatment, and that regimen ended on the discontinuation date or date of treatment change (i.e., augmentation or switching), whichever occurred first. Each treatment regimen change or start of a new regimen was considered to be a LOT change. Changes in any agent (‘targeted’ or chemotherapy) within 60 days of first treatment was not considered a LOT change.
A treatment gap was the number of days from the last day of supply to next date of dispensing, with a maximum allowable gap of 90 days. SCT before the end of a gap added a 6-month allowed gap. No medication refilled within the maximum allowed gap after supply days expired was considered to be a treatment discontinuation. Medications identified from the Healthcare Common Procedure Coding System (HCPCS) codes used the number of days supplied from the recommended treatment schedule.
Augmentations were when a patient started a new MM medication recommended by the NCCN guideline within 60 days prior to discontinuation of any of the treatments in the current regimen. A switch was when a new MM medication recommended by the NCCN guideline was started and at least one medication in the current regimen was discontinued within 60 days of beginning the new medication. Addition of chemotherapy agents (e.g., cyclophosphamide, doxorubicin, melphalan) was considered to be a LOT change.
A treatment regimen was discontinued once all medication in the regimen (corticosteroids not considered) were discontinued or an augmentation/switching occurred. Use of maintenance therapy (e.g., lenalidomide or bortezomib monotherapy) within 6 months after SCT was not considered to be switching or a LOT change. The regimen discontinuation date was extended until the discontinuation of maintenance therapy.
Demographic and Clinical Characteristics
For each MM patient included in the study population, demographic and clinical characteristics, (including age, sex, health plan type, insurance type [Commercial or Medicare], US region of residence, Quan Charlson Comorbidity Index [QCI] score, and year of index date) were evaluated on their index date or during the 12-month baseline period.
Healthcare Resource Utilization and Associated Costs
Over the 12-month period prior to index date, all-cause and MM-related (i.e., claims including an ICD-9/10 code indicating an MM diagnosis) healthcare resource utilization (HCRU) costs and associated costs were examined for each patient. HCRU included the number of hospitalizations and days of inpatient stays, number of emergency room (ER) visits, number of outpatient visits, and number of pharmacy fills (all-cause only). Average MM-related healthcare costs were reported for inpatient cost, ER cost, outpatient cost, drug costs, drug infusion cost, SCT cost, and other healthcare costs.
The primary outcome measures of this study were all-cause and MM-related healthcare costs that occurred after a patient’s index date. These costs were reported as the mean cost per patient (such as total all-cause healthcare cost) or mean cost per patient per month (PPPM). Results are provided for the overall study cohort, in addition to the subset of patients who were < 65 years of age (Commercially insured), who made up the majority (91.2%) of the sample. The average monthly total all-cause healthcare costs per patient were also extrapolated to estimate the total all-cause healthcare costs incurred for up to 36 months after a patient’s index date.
All statistical analyses were descriptive and conducted using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA).