Клиническое и экономическое бремя лиц, получающих пособия по уходу за больными, с множественными миеломами и почечными расстройствами: исследование наблюдений.

1. Introduction

Renal impairment (RI) is a frequent complication in patients with multiple myeloma (MM). As per an estimate, almost 61% of patients develop RI within a median of 1.2 years of their initial MM diagnosis. [ 1 ] In general, patients with MM and RI have a poor prognosis than those without RI, including a higher mortality rate (2 times), with morbidity and a shorter median overall survival (mOS, 17 months vs 51 months). [ 2 ] Survival is poor (mOS: 10.2 months) in patients with MM who develop end-stage renal disease (ESRD) and require dialysis. [ 3 ] Additionally, the rapid development of RI and chronic kidney disease (CKD) in patients with MM may lead to requirement of kidney transplant for survival. [ 4 ] Moreover, RI in MM is associated with significantly higher economic and healthcare resource utilization (HCRU) burden than MM without the complication, mainly because of inpatient and outpatient medical services. [ 5 , 6 ]

Excess monoclonal free light chain production is usually related to RI in patients with MM. Given the clinical and economic impact, timely detection of RI and early initiation of effective antimyeloma therapy are crucial considerations in restoring kidney function by focusing on early and long-term reduction of monoclonal free light chain production. [ 3 ] As a result, clinicians seek prompt interventions to reverse severe RI because renal failure sustained for more than 2 weeks may limit the likelihood of recovery. [ 7 ]

Presently, available frontline and subsequent treatment options for patients with MM and RI include proteasome inhibitors (PIs, including bortezomib [BORT or V], carfilzomib [CARF], or ixazomib [IXA]), immunomodulatory drugs (IMiDs, including lenalidomide [LEN or R] or pomalidomide [POM]), and anti-CD38 monoclonal antibodies (mAbs, including daratumumab [DARA] and isatuximab). [ 8 , 9 ] The International Myeloma Working Group and the National Comprehensive Cancer Network (NCCN) recommends BORT-based regimens as the current standard of care for MM patients with acute renal insufficiency. [ 9 – 11 ] LEN is not generally recommended in frontline therapy for MM patients with RI. [ 12 ] Additionally, some evidence has shown improved clinical outcomes with DARA in patients with relapsed/refractory MM (RRMM) with RI. [ 13 ]

Renal complications in patients with MM contribute to serious comorbidities and are associated with poor outcomes such as survival. [ 14 ] Factors such as cast nephropathy, light chain deposition disease, or amyloidosis may contribute to the presence of RI. [ 15 ] Due to major developments in the therapeutic landscape, [ 7 , 13 , 16 , 17 ] the care of MM patients with RI has evolved into a complicated decision-making process, resulting in a wide range of therapy patterns. However, RI majorly affects therapeutic choices in patients with MM because of their limited ability to tolerate the treatment (dose reduction, duration of treatment, and doublet vs triplet treatment regimen). These treatment modifications in MM patients with RI may contribute to suboptimal therapeutic response. Besides, data on MM patients with RI are scarce and poorly documented in a real-world setting. Therefore, this retrospective study aimed to assess the clinical and economic outcomes, specifically in MM patients with RI, using the Medicare research identifiable files (RIFs) data with Part D linkage, which may assist in improving the clinical management of these high-risk and challenging-to-treat patients. This study estimated the clinical and economic outcomes in MM patients with RI at the time of the initial diagnosis before first line (1L) treatment initiation.

2. Methods

2.1. Data source

This claims-based study was conducted using data from the Medicare RIFs with Part D (i.e. Drug Event File) linkage from January 2006 through December 2018. The study received an institutional review board exemption and a waiver granted under the 45 Code of Federal Regulations (CFR) 164.512(i) from the New England Institutional Review Board.

2.2. Study design

This retrospective cohort study included adult patients (aged ≥ 18 years) newly diagnosed with MM who were on continuous Medicare coverage (Parts A, B, and D) and initiated first line (1L) MM treatment on or after January 01, 2012. The clinical and economic burden of MM patients with RI (RI MM cohort) was evaluated while using a general MM cohort as a reference point rather than comparing the 2 cohorts. By defining the cohorts based on RI status at baseline (i.e. prior to MM treatment initiation), the study aimed to assess the implication of RI on MM treatment by highlighting the clinical and economic burden of RI among MM patients. The patients were followed-up for a median duration of 24 months. The focus on renally impaired MM patients was aimed to address the scarcity of data in this patient population and to highlight the clinical and economic burden in the real-world setting.

Patients from the general MM cohort were classified in the RI MM cohort if they had (Fig. 1 )

Evidence of acute kidney failure along with an MM diagnosis on the same date, where MM diagnosis occurred no more than 3 months prior to MM treatment initiation (see Table S1, Supplemental Digital Content, http://links.lww.com/MD/M916 illustrates the diagnosis codes in medical claims used to identify patients with MM).

Evidence of the following at any time prior to MM treatment initiation: CKD stage IV–V or ESRD, renal dialysis, hypertensive CKD stage V or ESRD, hypertensive heart and CKD stage V or ESRD, or Medicare eligibility because of ESRD (see Table S2, Supplemental Digital Content http://links.lww.com/MD/M917 illustrates the diagnosis codes in medical claims to identify patients with RI).

Patients with evidence of a kidney transplant at any point prior to MM treatment initiation were excluded from the RI MM cohort.

Patients meeting the sample selection criteria were analyzed by line of therapy (LoT) for the first 4 LoTs for MM. The LoTs were defined based on the first treatment for MM (e.g. 1L index date), and the treatment regimen for a specific LoT was composed of any treatments for MM observed within 60 days of the index date. [ 18 ] The LoT was observed until treatment augmentation (add-on)/switch to a new MM treatment >60 days post first MM agent, [ 19 ] treatment discontinuation (i.e. drop off all agents of the treatment regimen for >90 days), [ 19 ] end of data availability, end of Part A/B/D coverage, or death, whichever occurred first (e.g. 1L therapy end). A restart of any or start of new MM agent(s) following the end of the previous LoT was considered a new LoT. The LoT included stem cell transplant (SCT) and maintenance post-SCT, if applicable. The same approach was used to identify second line (2L), third line (3L), and fourth line (4L).

For the 1L analysis, the 1L index date was the first observed treatment for MM of the treatment regimen (LoT initiation), the baseline period was 6 months before the index date, and the study period was from the index date to the end of 1L (described previously). A similar design was used in 2L, 3L, and 4L.

2.3. Study outcomes and statistical analysis

As this study was not aimed to compare 2 cohorts of patients and was descriptive in nature, only unadjusted estimates were reported without any statistical comparisons. Patient characteristics including demographics (age and sex) and Medicare coverage information (ESRD, disability status, and dual eligibility) at the index date as well as Charlson comorbidity index (CCI) score, MM-associated comorbidities (CRAB; calcium elevation [hypercalcemia], renal dysfunction/insufficiency, anemia, and bone abnormalities [skeletal-related events, SREs]), and physical conditions other than CRAB measured during baseline were reported by LoT from 1L to 4L using descriptive statistics.

Treatment patterns, including duration of treatment (DoT; from LoT initiation to end) and time to next treatment (TTNT; from LoT initiation to next LoT initiation); clinical outcomes (real-world progression-free survival [rwPFS] and real-world overall survival [rwOS]); HCRU, including inpatient days, days with outpatient services, home health services, skilled nursing facility (SNF) services, emergency department visits, and hospice stays (incidence rates per person per year [PPPY]); and healthcare costs, including pharmacy and medical service costs (adjusted for inflation using the US Medical Care Consumer Price Index from the Bureau of Labor Statistics from the US Department of Labor and reported in 2020 USD, per person per month [PPPM]) were reported by LoT from 1L to 4L using descriptive statistics. Continuous measurements were summarized as mean, standard deviation (SD), and median; categorical variables were presented as frequency and percentages.

Real-world progression-free survival and rwOS were assessed using Kaplan–Meier (KM) analysis. For rwPFS, patients were observed from the LoT initiation (i.e. index date) to the subsequent LoT initiation (as a proxy of disease progression, excluding SCT) or death or censored at the end of follow-up (first event between the end of data availability and the end of Part A/B/D coverage). For rwOS, patients were observed from the LoT initiation to death (event), or the observation period of patients was censored at the end of follow-up.

Given that BORT-based regimens are preferred in MM patients with acute renal insufficiency [ 9 – 11 ] rwPFS and rwOS were also assessed for the subgroup of patients receiving BORT with dexamethasone (Vd) in 1L.

3. Results

3.1. Clinical and demographic characteristics

Overall, 13,573 patients diagnosed with MM (general MM cohort) from the Medicare RIFs database were included in this study, of which 3386 (24.9%) patients were identified with RI (RI MM cohort). Among the patients of the RI MM cohort, 89% had chronic RI conditions and the remaining had acute RI conditions at baseline. Patients of the RI MM cohort were observed to be generally younger, with a lower proportion of females and a higher proportion of Medicare coverage for ESRD and disability, than the general MM cohort (Table 1 ).

The RI MM cohort presented higher CCI scores and MM-associated comorbidities (anemia, hypercalcemia, and RI) than the general MM cohort (Table 1 ). On stratifying patients by LoT, MM patients presented with more frequent MM-associated comorbidities at the time of 1L initiation than the patients of the RI MM cohort (Table 1 ). At baseline, the most prevalent non-MM-specific comorbidities reported among all patients were hypertension and chronic pain/fibromyalgia (see Table S3, Supplemental Digital Content, http://links.lww.com/MD/M918 illustrates distribution of calendar years and preexisting comorbidities in patients with RI and MM).

3.2. Treatment patterns

During the observation period, 3386 (100%) MM patients with RI were observed with 1L (RI MM cohort), of which 8.7% reported receiving SCT, 23.3% with 2L, 22.6% with 3L, and 21.6% with 4L. For each LoT, the DoT was numerically shorter for the RI MM cohort, particularly in 1L (mean ± SD in months: 8.90 ± 9.59 and 10.49 ± 11.56) than for the general MM cohort. Consistently, when 1L was stratified by SCT status, the DoT was numerically shorter (mean ± SD in months: 15.50 ± 12.83 and 17.52 ± 14.66) in patients who received SCT and for those who did not (mean ± SD in months: 8.32 ± 9.02 vs 9.78 ± 10.95) than in the general MM cohort. Among those with a subsequent LoT, the RI MM cohort had numerically shorter TTNT than the general MM cohort from 1L to 2L (mean ± SD in months: 12.50 ± 11.28 and 13.97 ± 12.23) and from 2L to 3L (mean ± SD in months: 8.96 ± 7.13 and 9.97 ± 7.69; data not presented).

The Vd-based regimen was the most commonly received regimen in the RI MM cohort at 1L (45.7%), whereas the LEN–dexamethasone (Rd)-based regimen was the most commonly reported in 2L (30.3%) and 3L (18.2%; Fig. 2 ). Among the RI MM cohort who underwent SCT in 1L (n = 293), 64.5% (n = 189) were observed without maintenance therapy, and LEN-based maintenance therapy was the most prevalent among those with maintenance (23.9%, n = 70; see Table S4, Supplemental Digital Content, http://links.lww.com/MD/M919 illustrates patient characteristics based on subgroup analyses). The proportion of patients receiving DARA + BORT-based regimens was observed to have increased in the RI MM cohort for those who progressed from 2L to 4L therapy (1.1% to 6.8%). In addition, 10.9%, 7.8% to 14.6%, and 12.5% of patients received newer MM therapies, namely, DARA, CARF, and POM, respectively, in 3L and 4L (Fig. 2 ).

The most prevalent treatment regimen in the general MM cohort was Vd-based regimen in 1L (33.1%), whereas Rd-based regimen was most commonly reported in 2L (30.1%) and 3L (17.5%) and POM (13.3%) in 4L. For those who received SCT (n = 1332) and for those without SCT (n = 12,241) in 1L, the most prevalent regimens included BORT–LEN–SCT (23.0%) and Vd-based regimens (36.7%), respectively. Among patients who received SCT in 1L, 42.0% patients received a maintenance therapy.

3.3. Clinical outcomes

Median rwPFS and rwOS declined as the LoT progressed in the RI MM cohort. Median rwPFS and rwOS appeared numerically shorter at any LoT, especially in 1L (progression-free survival [PFS]: 12.9 and 16.4 months; overall survival [OS]: 31.1 and 46.8 months), for the RI MM cohort than for the general MM cohort (Table 2 ). Once stratified by SCT status, similarly, the RI MM cohort with SCT in 1L appeared to have numerically poorer mPFS and mOS (23.7 and 38.2 months, respectively) than the general MM cohort with SCT in 1L (28.3 and 62.6 months, respectively; data not presented).

The RI MM cohort receiving Vd in 1L had numerically shorter mPFS and mOS (10.3 and 28.4 months, respectively) than other RI MM cohorts at 1L (12.9 and 31.1 months, respectively; data not presented). The RI MM cohort receiving SCT and LEN maintenance therapy in 1L had numerically longer mPFS and mOS (55.1 and 82.3 months, respectively) than those with SCT without maintenance (18.8 and 28.0 months, respectively; data not presented).

3.4. Healthcare resource utilization and costs

Among patients of the RI MM cohort, the incidence of all-cause HCRU was higher in 1L than in other LoTs and appeared to increase from 2L to 4L (Table 3 ). In addition, the RI MM cohort had a numerically higher annual incidence of days with outpatient services (63.1 and 55.9 days, respectively), inpatient days (12.1 and 7.8 days, respectively), home health services (9.2 and 5.2 days, respectively), and SNF services (2.7 and 1.4 days, respectively) in 1L than the general MM cohort. A consistent numerically higher incidence of these HCRU was observed across subsequent LoTs in the RI MM cohort than in the general MM cohort (Table 3 ). A substantial proportion of the inpatient days incurred by the RI MM cohort was related to RI management (>68% of inpatient days with a diagnosis of RI at any LoT). The annual incidence of days with dialysis increased from 49 to 128 days in the RI MM cohort from 1L to 4L.

The mean all-cause total costs (in USD) increased from 1L to 4L in the RI MM cohort (Fig. 3 ). Numerically, total costs in the RI MM cohort were slightly higher than those observed in the general MM cohort across each LoT. The key driver of this total cost was the additional medical service cost ($10,457 for RI and $7997 for the general MM cohort in 1L) incurred by patients (Fig. 3 ). Medical costs in 1L were mainly driven by inpatient costs (48% of medical costs) in the RI MM cohort. Descriptively, these inpatient costs remained higher for the RI patients than for the general MM cohort at any LoT (Fig. 3 ). The MM treatment costs were lower in the 1L than that in 2L to 4L for RI MM patients and numerically lower than those for the general MM cohort in 1L, which may be explained by the significant proportion of RI MM patients using Vd (45.7%) or BORT (Velcade™)+ cyclophosphamide (CYCLO) + dexamethasone (VCd, 12.1%) in 1L (Fig. 2 ) and a substantial proportion of the general MM cohort using LEN-based regimens in 1L (VRd [26.9%]), Rd (20.8%), BORT–LEN–SCT 2.3%); 2L (Rd [30.1%]); and 3L (Rd [17.5%]).

4. Discussion

This study describes a diverse treatment landscape for MM patients with RI in a nationwide cohort of 3386 Medicare patients treated with various therapies between 2012 and 2018 in the United States. Vd-based regimen was the essential 1L treatment for the RI MM cohort during the study period. This is in line with recent recommendations from NCCN and IMWG. [ 10 ] LEN was a more prevalent treatment in the RI MM cohort which reached 2L or 2L+. Similar to the general MM cohort, BORT and LEN were prevalent during earlier LoTs in the RI MM cohort, which decreased over later LoTs. This real-world study showed increasing usage of novel MM therapies, such as CARF, POM, and DARA in MM patients with RI at 3L and 4L since their introduction.

In this study, the RI MM cohort required earlier escalation to the next LoT than the general cohort. Additionally, DoT and TTNT of existing therapeutic regimens generally decreased in later LoTs, depicting the decrease of clinical benefits over time. Similar findings were reported in the RI MM cohort in the Swedish population. [ 20 ] As the RI MM cohort goes through each LoT faster, DoT/TTNT decreases with LoTs; thus, the use of newer treatments in earlier LoT may provide potential clinical benefits.

Considering the impact of RI on patients with MM, the cohorts in the present study were categorized based on the baseline RI status of patients. Patients with preexisting renal conditions such as CKD stages IV–V, ESRD, acute kidney failure along with an MM diagnosis, or evidence of a kidney transplant were included. However, patients with MM may develop RI as a complication during the disease due to which routine renal function assessments in patients with MM are critical. The onset of RI after the initiation of MM treatment may suggest lack of treatment effect and/or disease progression. From a treatment perspective, RI may affect therapy choice (e.g. doublet vs triplet regimen), and how well the patient may be able to stay on or tolerate the treatment (e.g. dose reduction, or duration of treatment might be short), which may result in suboptimal treatment outcome. Therefore, RI may be considered a treatment effect modifier rather than a prognostic factor. In this study, the implication of RI on MM treatment was assessed by highlighting the clinical and economic burden of RI among patients with MM.

Higher rates of MM-associated comorbidities in the RI MM cohort, supported by a higher mean CCI score, were also observed. Higher rates of MM-associated comorbidities decrease the treatment options and result in higher treatment costs. Previous real-world analysis reports from Australia and New Zealand Myeloma and Related Diseases Registry also reported similar findings, where the RI MM cohort had higher comorbidities than patients with normal renal function. [ 21 ] However, the SREs were similar for both groups, and these were consistent with findings reported by Bhowmik et al Although it has been observed that frontline treatment regimens improve outcomes in the RI MM cohort, the duration of preexisting comorbidities must be considered prior to treatment initiation. [ 5 ]

In the present study, the real-world mPFS and mOS were shorter for the RI MM cohort than the general MM cohort at all LoTs. The rwPFS and rwOS declined as the LoT progressed beyond the second LoT, possibly due to treatment discontinuation. For BORT, the mPFS was comparable with clinical studies (mPFS: 8.6 to 12.1 months). [ 22 – 24 ] However, mOS observed in the real world was lower than that reported in recent clinical trials (mOS: 25 to 30 months). [ 24 , 25 ] For 3L, mPFS and mOS declined compared with 1L and 2L, in accordance with the observed outcomes in clinical trials in the RI MM cohort who received POM + dexamethasone. [ 26 , 27 ] In the present study, the mPFS and mOS of the RI MM cohort receiving SCT followed by LEN maintenance therapy were longer than that of patients receiving SCT without maintenance therapy. These observations are in accordance with findings of previous studies where LEN maintenance after SCT offered improved OS in the RI MM cohort ( P = .008) [ 28 ] and the general MM cohort. [ 29 ] However, LEN maintenance therapy was associated with high treatment costs (mean costs $13,095 vs $8910 PPPM; P < .0001) and additional adjusted pharmacy costs (approximately $6000 PPPM) compared with the no-maintenance cohort. [ 30 ] This indicated a need for earlier initiation of newer therapeutic options, which may help improve rwPFS and rwOS, particularly in the RI MM cohort.

Findings from this study suggested that the RI MM cohort had higher HCRU at all LoTs than the general MM cohort. These results are consistent with previously published studies evaluating the economic burden in MM patients with RI. Bhowmik et al reported that inpatient admissions and emergency room (ER) visits were higher in MM patients with CKD. [ 5 ] Overall, a greater increase in all-cause total costs for patients of the RI MM cohort was observed than that for the general MM cohort, with each subsequent LoT. LoT increases are associated with higher treatment costs for the RI MM cohort, suggesting that such patients with more severe disease, a higher risk of comorbidities, and a more severe form of MM may require more healthcare resources than MM patients without RI, leading to higher treatment costs.

The healthcare costs in the RI MM cohort were mainly driven by the medical cost, accounting for 72% of the total costs. The inpatient costs are important as they contribute to approximately one-half of medical costs. This high contribution of inpatient costs to medical costs is in accordance with the higher number of inpatient days. At initial LoTs, outpatient and inpatient costs are the main drivers of medical costs. It is important to note that higher economic burden among patients with RI MM may be associated with poorer treatment outcomes such as faster disease progression and higher comorbidities. These results have been consistent with other studies evaluating patients with RI MM. These results are comparable with the study by Medhekar et al, [ 6 ] who reported that RI has a significant economic burden in MM patients, with high all-cause HCRU (higher inpatient and outpatient costs) using MarketScan ® databases from 2006 to 2016. Another retrospective cohort study using MarketScan ® database reported that the total cost of treating RI MM cohort was higher than that of matched controls without RI; the difference was driven by total medical costs (outpatient and inpatient costs). [ 5 ] The contribution of pharmacy and MM treatment costs were lower in total cost, possibly because of the lower cost of BORT as it remains the essential therapeutic regimen during 1L treatment in MM patients with RI compared with LEN-based regimen, which was the most prevalent treatment regimen in general MM cohort. These results indicated that the economic burden of treating RI MM cohort is substantially high.

4.1. Strengths and limitations

Although several studies have evaluated the HCRU and healthcare costs in patients with MM, there is a lack of published evidence reporting these outcomes among MM patients with RI. [ 5 , 6 ] This is one of the first studies to focus on this patient population, and the first to describe HCRU and healthcare costs based on 1L to 4L therapy in the RI MM cohort in the United States. Another strength of this study lies in the large sample size, covering a heterogenous nationwide patient population based on the Medicare data.

Some limitations of this retrospective analysis of claims data should be considered. The findings should be interpreted in the context of the sample selection criteria; therefore, results may not represent the MM patients with commercial or no health insurance. Claims data in real-world analyses inherently reflect the individual decisions of physicians as they evaluate and treat patients, which differ from the controlled and standardized methods used in clinical studies. The present algorithm was carefully developed in collaboration with a clinical expert to represent LoT observed in clinical practice. Additionally, the use of corticosteroids in treatment regimens was not reported because their use could not be accurately assessed based on claims data alone; a patient might not have submitted claims for corticosteroids because of cash payment or pharmacy discount programs. [ 18 , 31 ] Therefore, all lines were assumed to be with corticosteroids. The reasons for switching to a subsequent treatment or LoT initiation or discontinuation were not available from the claims data. The initiation of the next LoT was used as a proxy for PFS (in addition to the death event), which could have led to misclassifications of toxicity-based treatment switches as an indication of disease progression. Laboratory results, risk stratification of MM cases, and clinical information (e.g. disease stage, cytogenetic risk status, and performance status) were not available from the claims data. Data reported using healthcare claims database in this study were until 2018, which may be considered a limitation. However, given the 2-year lag of Medicare data and the gap in published evidence on the RI MM patient population, we believe this study would still add valuable insight to the knowledge base. Lastly, this study was subject to common limitations of studies on the basis of healthcare claims data, including occasional coding errors or inaccurate/missing data on prescriptions, diagnoses, and limited information on some important clinical characteristics.

5. Conclusion

This real-world study investigated treatment patterns, clinical outcomes, and associated healthcare expenditures of MM patients with RI. Patients with MM who had baseline RI were shown to experience higher clinical and economic burdens in real-world clinical practice than the general MM population. The findings demonstrate a considerable unmet need in these patients. Real-world survival outcomes of the RI MM cohort receiving SCT followed by LEN maintenance therapy were longer than that of patients receiving SCT without maintenance therapy, suggesting that the usage of high-efficacy and newer therapies early in the treatment pathway of MM patients with RI may result in better clinical outcomes despite higher costs. Further research investigating the benefit–risk profiles, with early initiation of therapeutic regimens, may help address an unmet need in a high-risk and difficult-to-treat RI MM cohort.

Acknowledgments

Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Pranshu Roy and Amit D. Kandhare, of Sanofi in accordance with Good Publication Practice guidelines.

Author contributions

Conceptualization: Peggy Lin, Annie Guerin, Medha Sasane.

Data curation: Dominick Latremouille-Viau, Annie Guerin, Medha Sasane.

Formal analysis: Dominick Latremouille-Viau, Annie Guerin.

Funding acquisition: Medha Sasane.

Investigation: Peggy Lin.

Methodology: Parameswaran Hari, Peggy Lin, Medha Sasane.

Project administration: Peggy Lin, Medha Sasane.

Resources: Peggy Lin, Medha Sasane.

Supervision: Parameswaran Hari, Peggy Lin, Medha Sasane.

Validation: Parameswaran Hari.

Visualization: Medha Sasane.

Writing – original draft: Parameswaran Hari, Dominick Latremouille-Viau, Peggy Lin, Annie Guerin, Medha Sasane.

Writing – review & editing: Parameswaran Hari, Dominick Latremouille-Viau, Peggy Lin, Annie Guerin, Medha Sasane.

Supplementary Material

Abbreviations: 1L first line 2L second line 3L third line 4L fourth line BORT bortezomib CARF carfilzomib CCI Charlson comorbidity index CFR Code of Federal Regulations CIS cisplatin CKD chronic kidney disease CRAB calcium elevation (hypercalcemia), renal dysfunction/insufficiency, anemia, and bone abnormalities CYCLO cyclophosphamide DARA daratumumab DoT duration of treatment DOX doxorubicin ELO elotuzumab ER emergency room ESRD end-stage renal disease FLC free light chain HCRU healthcare resource utilization HDAC histone deacetylase ICD-10-CM International Classification of Diseases Tenth Revision-Clinical Modification ICD-9 International Classification of Diseases Ninth Revision IMiD immunomodulatory drug IXA ixazomib KM Kaplan–Meier LEN lenalidomide LoT line of therapy mAb monoclonal antibody MM multiple myeloma mOS median overall survival mPFS median progression-free survival NCCN National Comprehensive Cancer Network OS overall survival PFS progression-free survival PI proteasome inhibitor POM pomalidomide PPPM per person per month PPPY per person per year Rd LEN–dexamethasone RI renal impairment RIF research identifiable file RRMM relapsed/refractory multiple myeloma rwOS real-world overall survival rwPFS real-world progression-free survival SCT stem cell transplant SD standard deviation SNF skilled nursing facility SRE skeletal-related event THAL thalidomide TTNT time to next treatment VCd velcade™ + cyclophosphamide + dexamethasone Vd dexamethasone VRd velcade™ + Revlimid + dexamethasone.

This study was funded by Sanofi.

All patients, service users, or participants in any type of qualitative or quantitative research have given their informed consent to participate in this research.

The study received an institutional review board exemption and a waiver granted under the 45 Code of Federal Regulations (CFR) 164.512(i) from the New England Institutional Review Board.

The authors have no conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplemental Digital Content is available for this article.

How to cite this article: Hari P, Latremouille-Viau D, Lin P, Guerin A, Sasane M. Clinical and economic burden of medicare beneficiaries with multiple myeloma and renal impairment: An observational study. Medicine 2024;103:26(e38609).

Parts of these data using a previous Medicare data cut were presented as a poster at the 62nd ASH Annual Meeting & Exposition, December 5–8, 2020 (Abstract #134597). Blood . 2020;136(Suppl 1):17–18. Congress URL: https://www.hematology.org/meetings/annual-meeting .

Contributor Information

Dominick Latremouille-Viau, Email: Dominick.Latremouille-Viau@analysisgroup.com.

Peggy Lin, Email: Peggy.Lin@sanofi.com.

Annie Guerin, Email: annie.guerin@analysisgroup.com.

Medha Sasane, Email: medha.sasane@sanofi.com.

References

[1] Bhowmik D, Qian Y, Bond TC, et al. Prevalence of renal impairment in patients with multiple myeloma: analysis of real-world database. Value Health. 2016;19:A141.

[2] Chen X, Luo X, Zu Y, et al. Severe renal impairment as an adverse prognostic factor for survival in newly diagnosed multiple myeloma patients. J Clin Lab Anal. 2020;34:e23416.

[3] Yadav P, Cook M, Cockwell P. Current trends of renal impairment in multiple myeloma. Kidney Dis (Basel). 2016;1:241–57.

[4] Qian Y, Bhowmik D, Bond C, et al. Renal impairment and use of nephrotoxic agents in patients with multiple myeloma in the clinical practice setting in the United States. Cancer Med. 2017;6:1523–30.

[5] Bhowmik D, Song X, Intorcia M, Kent ST, Shi N. Healthcare resource use and costs associated with chronic kidney disease in US private insurance patients with multiple myeloma. J Oncol Pharm Pract. 2019;25:855–64.

[6] Medhekar R, Gilligan AM, Kent ST, Feng C, Henriques C. Healthcare resource utilization (HRU) and costs associated with renal impairment (RI) among treated multiple myeloma (MM) patients. J Clin Oncol. 2018;36(15_suppl):e18922–e18922.

[7] Capra M, Martin T, Moreau P, et al. Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis. Haematologica. 2022;107:1397–409.

[8] Fava A, Fulladosa X, Montero N, et al. Treatment of multiple myeloma with renal involvement: the nephrologist’s view. Clin Kidney J. 2018;11:777–85.

[9] Dimopoulos MA, Mikhael J, Terpos E, et al. An overview of treatment options for patients with relapsed/refractory multiple myeloma and renal impairment. Ther Adv Hematol. 2022;13:20406207221088458.

[10] Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016;34:1544–57.

[11] Piro E, Molica S. A systematic review on the use of bortezomib in multiple myeloma patients with renal impairment: what is the published evidence? Acta Haematol. 2011;126:163–8.

[12] Kastritis E, Dimopoulos MA. The evolving role of lenalidomide in the treatment of hematologic malignancies. Expert Opin Pharmacother. 2007;8:497–509.

[13] Turgutkaya A, Bolaman AZ, Yavaşoğlu I. Experience of daratumumab in six patients with multiple myeloma and kidney failure. Plasmatology. 2021;15:26348535211042012.

[14] Faiman BM, Mangan P, Spong J, Tariman JD; The International Myeloma Foundation Nurse Leadership Board. Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board. Clin J Oncol Nurs. 2011;15 Suppl(Suppl):66–76.

[15] Kundu S, Jha SB, Rivera AP, et al. Multiple myeloma and renal failure: mechanisms, diagnosis, and management. Cureus. 2022;14:e22585.

[16] Dimopoulos MA, Leleu X, Moreau P, et al. Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis. Leukemia. 2021;35:562–72.

[17] Kumar SK, et al. NCCN guidelines® insights: multiple myeloma, version 3.2022. J Natl Compr Canc Netw. 2022;20:8–19.

[18] Chen CC, Parikh K, Abouzaid S, et al. Real-world treatment patterns, time to next treatment, and economic outcomes in relapsed or refractory multiple myeloma patients treated with pomalidomide or carfilzomib. J Manag Care Spec Pharm. 2017;23:236–46.

[19] American Cancer Society. 2021. [cited 2021 December 22,]; https://www.cancer.org/cancer/multiple-myeloma/treating/chemotherapy.html .

[20] Uttervall K, Duru AD, Lund J, et al. The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment. PLoS One. 2014;9:e101819.

[21] Ho PJ, Moore EM, McQuilten ZK, et al. Renal impairment at diagnosis in myeloma: patient characteristics, treatment, and impact on outcomes. Results from the Australia and New Zealand myeloma and related diseases registry. Clin Lymphoma Myeloma Leuk. 2019;19:e415–24.

[22] Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica. 2015;100:e207–10.

[23] Ludwig H, Adam Z, Hajek R, et al. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol. 2010;28:4635–41.

[24] Ponisch W, Moll B, Bourgeois M, et al. Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with relapsed or refractory multiple myeloma and light chain-induced renal failure. J Cancer Res Clin Oncol. 2013;139:1937–46.

[25] San-Miguel JF, Richardson PG, Sonneveld P, et al. Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study. Leukemia. 2008;22:842–9.

[26] Weisel K, Dimopoulos MA, Cavo M, et al. Pomalidomide + low-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma and renal impairment: analysis of patients from the phase 3b stratus trial (MM-010). Blood. 2014;124:4755–4755.

[27] Dimopoulos M, Weisel K, van de Donk NWCJ, et al. Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and renal impairment: results from a phase II trial. J Clin Oncol. 2018;36:2035–43.

[28] Baertsch MA, Mai EK, Hielscher T, et al.; German-Speaking Myeloma Multicenter Group (GMMG). Lenalidomide versus bortezomib maintenance after frontline autologous stem cell transplantation for multiple myeloma. Blood Cancer J. 2021;11:1.

[29] McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279–89.

[30] Hari P, Ung B, Abouzaid S, Agarwal A, Parikh K. Lenalidomide maintenance post-transplantation in newly diagnosed multiple myeloma: real-world outcomes and costs. Future Oncol. 2019;15:4045–56.

[31] Tungol A, Starner CI, Gunderson BW, Schafer JA, Qiu Y, Gleason PP. Generic drug discount programs: are prescriptions being submitted for pharmacy benefit adjudication? J Manag Care Pharm. 2012;18:690–700.

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