Burden of CRAB Events By Relapse in Patients with Newly Diagnosed Multiple Myeloma Not Eligible for Stem Cell Transplant

Background: For decades, CRAB criteria (hypercalcemia, renal impairment, anemia, and bone disease) have been used to diagnose multiple myeloma (MM), but little is known about the economic burden of CRAB in patients with MM who have relapsed. The only category 1 doublet regimens recommended by NCCN Guidelines for non-transplant candidates are lenalidomide-based (NCCN Myeloma v4.2018). This study aims to evaluate CRAB event rates and the associated economic burden among newly diagnosed MM (NDMM) patients on doublet therapy who were not eligible for stem cell transplant (SCT) and were followed to next line of therapy.

Methods: This retrospective study identified patients with ≥ 2 claims of MM (ICD-9-CM code: 203.0x; ICD-10-CM code: C90.0x) ≥ 30 days apart and ≥ 1 treatment (first claim date was used as index date) between January 1, 2011 and December 31, 2015 from the Medicare database. Eligible patients were required to have continuous enrollment from 6 months pre-index or first MM diagnosis date until ≥ 12 months post-index date unless patients died < 12 months post-index date (the follow-up period); ≥ 1 full cycle of therapy; no evidence of prior MM diagnosis or treatment (including autologous SCT [ASCT]); and no evidence of ASCT in the follow-up period. First line of therapy (LOT1) included all treatments prescribed within 60 days of the index date, and patients were included in the doublet therapy cohort based on the index treatment regimen. Progression to a subsequent LOT (LOT2) was defined by the earliest occurrence of an addition or switch to new non-maintenance treatment > 60 days post-index date, restart of any non-maintenance MM treatment after a > 180-day gap, or a dose increase from maintenance to relapse therapy. CRAB event rate per 1,000 person-years (PYs), CRAB event-related healthcare resource utilization (HRU) per patient per month (PPPM), and costs PPPM were evaluated during the LOT1 (the time from index date to end of LOT1) and LOT2 (the time from initiation of LOT2 to end of LOT2) among patients on doublet therapy with LOT1 and those who progressed to LOT2, respectively. Mean was calculated for the continuous variables, while categorical variables were presented as percentage values. Since the LOT2 population was a subset of the LOT1 population and they were not mutually exclusive cohorts, no statistical comparisons were made.

Results: The study included 4,970 patients with MM not eligible for ASCT, of which 3,065 (61.7%) patients were prescribed doublet therapy in LOT1. Among these patients on doublet therapy, 1,122 (36.6%) initiated LOT2. The mean age was approximately 77 years, and most patients were white (LOT1, 77.0%; LOT2, 79.7%). The majority of the patients had hypertension (LOT1, 88.3%; LOT2, 86.1%), followed by anemia (LOT1, 79.0%; LOT2, 75.6%) and osteoarthritis (LOT1, 75.7%; LOT2, 76.7%), as comorbidities during the 6 months prior to the index date. CRAB event rates declined from LOT1 to LOT2, with the highest event rate per 1,000 PYs observed for anemia (LOT1, 1,965.1; LOT2, 1,808.2), followed by bone disease (LOT1, 258.1; LOT2, 244.1), renal impairment (LOT1, 167.9; LOT2, 159.9), and hypercalcemia (LOT1, 106.9; LOT2, 99.6); a decline in event rate was observed from LOT1 to LOT2 (Figure 1). CRAB event-related HRU PPPM increased from LOT1 to LOT2, including number of inpatient visits (LOT1, 0.1; LOT2, 0.2), length of inpatient stay (LOT1, 0.8 days; LOT2, 1.0 days), and number of outpatient hospital visits (LOT1, 2.0; LOT2, 2.2). However, the number of outpatient office visits PPPM decreased from LOT1 to LOT2 (LOT1, 0.9; LOT2, 0.8). Similarly, there was a trend toward increased CRAB event-related healthcare costs PPPM from LOT1 to LOT2 (Figure 2) including inpatient (LOT1, USD 1,548; LOT2, USD 2,031), outpatient hospital (LOT1, USD 214; LOT2, USD 301), outpatient office (LOT1, USD 77; LOT2, USD 89), and total medical costs (LOT1, USD 2,120; LOT2, USD 2,593).

Conclusions: This study shows that CRAB events were more expensive to treat as patients relapse. Delaying disease progression may be associated with lower HRU and potential cost savings, thereby reducing the burden of MM. A potential limitation of this study is that claims data do not include clinical parameters. Future studies should be considered to evaluate the impact of age and comorbidities on the economic burden associated with CRAB events. This study also highlights the value of delaying progression and the time to next treatment.

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