Multiple myeloma (MM) is a serious hematologic malignancy affecting plasma cells, leading to various complications including anemia, neutropenia, thrombocytopenia, bone loss, fractures, and kidney disease. In the US, approximately 32,270 new cases are diagnosed annually, with a five-year survival rate of about 54%. Current treatment guidelines recommend initiating therapy upon symptom onset or biomarker identification. Treatment for transplant-eligible (TE) patients is individualized, often involving combination therapies with corticosteroids, proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), and chemotherapy. Relapse and refractory MM require further treatments, but response rates decrease with each line of therapy. While previous studies have shown substantial costs associated with MM treatment, particularly in subsequent lines of therapy, research specifically focusing on the economic burden for MM patients who received an SCT is lacking. This study aims to address this gap by comparing HRU and healthcare costs between MM patients with and without progression who have received at least one LOT, including an SCT, using inverse probability of treatment weights (IPTW) to account for baseline characteristic differences.

Several retrospective observational studies have previously documented significant costs associated with MM patients undergoing second-line or subsequent treatments. These studies focus primarily on patients progressing and requiring additional lines of therapy. However, there is a lack of evidence specifically addressing the economic burden for MM patients who have undergone an SCT. One notable prior study by Hagiwara et al. examined transplant-ineligible MM patients and found that total annual healthcare costs were substantially higher for patients with progression compared to those without progression across multiple lines of therapy (L1-L4). This current study builds upon this previous work by focusing on a transplant-eligible population using a similar methodology, but adapting the algorithm for identifying LOTs to account for the SCT.

This retrospective incident user cohort study utilized data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) and Medicare and Coordination of Benefits (MDCR) databases. The study included adult patients with a confirmed MM diagnosis (at least one inpatient claim with MM ICD code or at least two outpatient claims within 30-365 days) between January 1, 2006, and September 30, 2018. Inclusion criteria included initiating MM therapy (lenalidomide, pomalidomide, thalidomide, bortezomib, carfilzomib, ixazomib, daratumumab, elotuzumab, panobinostat, or vorinostat) and receiving an SCT within one year of diagnosis. Exclusion criteria included prior MM therapy, simultaneous use of multiple PIs, missing supply information, and missing demographics. Lines of therapy (LOTs) were identified using an adapted algorithm previously published for transplant-ineligible patients. Progression status was determined using a 12-month event identification period after LOT initiation, defined as advancement to the next LOT, evidence of bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal-related events, fractures, acute kidney disease, renal failure, or death. An index date was assigned (30 days prior to documented progression for progressing patients; randomly assigned for non-progressing patients to match time from treatment initiation). Baseline characteristics were assessed 12 months prior to the index date. Annual HRU (emergency department visits, outpatient visits, prescription claims, inpatient admissions, and inpatient days) and total healthcare costs were calculated for each patient and LOT. Stabilized inverse probability of treatment weights (sIPTW) were used to adjust for differences in baseline characteristics. Average treatment effect (ATE) weights were employed and adjusted for follow-up duration. Expected cumulative total plan costs were estimated using the Kaplan-Meier sampling average (KMSA) method. A subgroup analysis was performed for LOTs initiated before and after 2013 to evaluate temporal trends.

Of the 5309 MM patients who received MM therapies (including SCT) during the study period, 3599 qualified. Among these, 934 patients experienced progression in L1, and 2665 did not. Matched pairs were created for analysis (904 in L1, 482 in L2, 244 in L3). Patients with progression were older and had more comorbidities. The mean number of hospitalizations per year was significantly greater for patients with progression than for those without in all LOTs (differences ranging from 0.32 to 0.97). Similarly, mean annual outpatient visits were higher in all LOTs for patients with progression. Annual MM therapy costs were generally lower for patients with progression, possibly due to treatment discontinuation following disease progression events. However, total annual healthcare costs were significantly higher for patients with progression across all LOTs (incremental annual costs ranging from $18,359 to $87,055). The incremental annual costs were largely attributed to MM-related expenses. Cumulative total plan costs at 1-year post-index were substantially higher for patients with progression in all LOTs. Subgroup analysis revealed similar trends in both pre- and post-2013 LOT initiation periods, with higher HRU and costs for patients with progression. However, the magnitude of the cost differences varied between the periods.

This study demonstrates a significant economic burden associated with disease progression in MM patients receiving SCT and systemic therapy. Increased HRU and costs were observed across all LOTs and outcome measures, except for MM therapy costs in L1-L3, potentially reflecting treatment discontinuation due to progression events. The findings highlight the impact of early relapse and aggressive disease on healthcare resource utilization and costs. The results are consistent across the study period, both before and after 2013. These results suggest that therapies designed to delay progression in MM patients could lead to substantial cost savings, a factor that should be considered when evaluating innovative MM treatments.

This study confirms a significant increase in healthcare costs and resource utilization for MM patients with disease progression within 12 months of treatment initiation, regardless of the line of therapy. This emphasizes the substantial economic burden of early relapse and aggressive disease. Treatments aimed at delaying progression could significantly reduce downstream costs and should be a key factor in assessing the value of novel MM therapies. Future research should focus on validating these findings and explore the cost-effectiveness of treatments impacting disease progression.

This study is based on administrative claims data, which has inherent limitations including potential misidentification of study subjects, coding errors, and lack of sensitivity and specificity in diagnosis and procedure codes. Participation in clinical trials or patient assistance programs might have led to underreporting of costs. The MarketScan database, while geographically diverse, may not represent all US patients. Although inverse probability of treatment weighting was used, unmeasured confounding factors remain a possibility. The algorithm used for identifying lines of therapy, though based on previous studies, lacks clinical validation. The definition of progression using surrogate markers might have underestimated the actual number of progression events.