This retrospective, observational, cohort study included data from the nationwide US Optum® de-identified electronic health record (EHR) database. The dataset includes all data collected from January 1, 2006, to December 31, 2019. The dataset is statistically deidentified under the Expert Determination method consistent with the Health Insurance Portability and Accountability Act and managed according to Optum’s customer data use agreements. This article is based on previously collected data and does not contain any studies with human participants or animals performed by any of the authors.
Inclusion and exclusion criteria are described in Table 1. In this study, patients were included if they had ≥ 2 medical records with a diagnosis of MM at least 30 days apart but no more than 365 days apart. The first of these two medical records was considered the diagnosis date. Patients were aged ≥ 18 years as of the first observed treatment for MM. Patients had ≥ 1 medical record for a medical service with a procedure code or a prescription for an MM treatment, including immunomodulatory drugs (i.e., thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (PIs; i.e., bortezomib, carfilzomib, ixazomib), histone deacetylase inhibitors (i.e., panobinostat), monoclonal antibodies (i.e., daratumumab, elotuzumab, isatuximab), chemotherapy (i.e., bendamustine, cisplatin, cyclophosphamide, doxorubicin, etoposide, liposomal doxorubicin, melphalan), or other treatments (i.e., selinexor, an inhibitor of nuclear export). Patients were included if they initiated the first MM treatment ≤ 1 month prior to or any time after the MM diagnosis date, and if they initiated first-line therapy for first observed treatment for MM on or after January 1, 2012. Patients were enrolled in an integrated delivery network and must have had at least one medical activity within 12 months prior to the index date (date of initiation of the line of therapy) and at least one medical activity within 2 months after the index date.
Patients were excluded if any of the following criteria were met: an indicator of enrollment in a clinical trial on or after the first observed treatment for MM, ≥ 2 medical records on different days with a diagnosis for a blood cancer other than MM at any time, ≥ 1 medical record with a diagnosis for neoplasm of unspecified nature on or after the first observed treatment for MM, ≥ 2 medical records with a diagnosis for malignant neoplasm ≤ 2 years prior to the first observed treatment for MM, an indicator of stem cell transplant (SCT) prior to the first observed treatment for MM, ≥ 1 medical record with a diagnosis for relapsed MM or MM in remission prior to the first observed treatment for MM, or first-line treatment with melphalan or doxorubicin (with or without corticosteroids) before an indicator of SCT.
For time to next treatment, an event was defined as the start of the subsequent line of therapy, which was the date of the first occurrence of (a) treatment switch, (b) treatment add-on, (c) resumption of MM treatment (old or new regimen) after a treatment discontinuation (a drop of all therapeutic agents of the treatment regimen for > 90 days), or (d) death. For overall survival, an event was defined as death.
To be included in the asthma group, patients had ≥ 1 medical record with a diagnosis for asthma during the 12-month baseline period prior to initiating treatment. To be included in the COPD group, patients had ≥ 1 medical record with a diagnosis for COPD during the 12-month baseline period prior to initiating treatment. To be included in the asthma or COPD group, patients had ≥ 1 medical record with a diagnosis for asthma or COPD during the 12-month baseline period prior to initiating treatment.
Patient characteristics were summarized by line of therapy for the first four lines of therapy and replicated separately among the following subgroups: (a) patients with COPD, (b) patients without COPD, (c) patients with asthma, (d) patients without asthma, (e) patients with either asthma or COPD (asthma/COPD), and (f) patients with neither asthma nor COPD. Mean, standard deviation, and median are presented for continuous variables, and the frequency and percentage are presented for categorical variables.
For time-to-next-treatment analyses, patients were observed from the line of therapy initiation to start of the subsequent line of therapy. Patients without a subsequent line of therapy were censored at the earliest of death, the date of their last medical activity, or the end of the study period. For overall survival analyses, patients were observed from the line of therapy initiation to date of death, or patients without an observed date of death were censored at the end of the study period or the date of last medical activity.
Patients with asthma, COPD, or asthma/COPD were compared with patients without asthma, COPD, or asthma/COPD for time to next treatment and overall survival using a one-sided log-rank test stratified by age. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for time to next treatment and overall survival, adjusted for age, sex, race, geographic region, insurance type, and Quan–Charlson comorbidity index (QCCI).