Association between Low-income Subsidies and Inequities in Orally-administered Antimyeloma Therapy Use

Abstract

Objectives:

The Medicare Part D low-income subsidy program drastically reduces patient cost-sharing and may improve access to and equitable use of high-cost antimyeloma therapy. We compared initiation of and adherence to orally-administered antimyeloma therapy between full subsidy and non-subsidy enrollees and assessed the association between full subsidies and racial/ethnic inequities in orally-administered antimyeloma treatment use.

Study Design:

Retrospective cohort study.

Methods:

We used Surveillance, Epidemiology, and End Results-Medicare data to identify beneficiaries diagnosed with multiple myeloma between 2007 and 2015. Separate Cox proportional hazards models assessed time from diagnosis to treatment initiation and time from therapy initiation to discontinuation. Modified Poisson regression examined therapy initiation in the 30, 60, and 90 days following diagnosis and adherence to and discontinuation of treatment in the 180 days following initiation.

Results:

Receipt of full subsidies was not associated with earlier initiation of or improved adherence to orally-administered antimyeloma therapy. Full subsidy enrollees were 22% (adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] 1.08–1.38) more likely to experience earlier treatment discontinuation than non-subsidy enrollees. Receipt of full subsidies did not appear to reduce racial/ethnic inequities in orally-administered antimyeloma therapy use. Black full subsidy and non-subsidy enrollees were 14% (aHR 0.86, 95% CI 0.73–1.02 and aHR 0.86, 95% CI 0.74–0.99, respectively) less likely than their White counterparts to ever-initiate treatment.

Conclusions:

Full subsidies alone are insufficient to increase uptake or equitable use of orally-administered antimyeloma therapy. Addressing known barriers to care (e.g., social determinants of health, implicit bias) could improve access to and use of high-cost antimyeloma therapy.

PRECIS:

Medicare Part D low-income subsidies alone are insufficient to improve the uptake and equitable use of high-cost, orally-administered antimyeloma therapy.

INTRODUCTION

Increasing pharmaceutical prices¹ and variations in cost-sharing across the phases of Medicare Part D² have raised concerns about patients’ financial burden and the suboptimal use of orally-administered antimyeloma therapy.^1,3,4 Specifically, 29% of patients with high out-of-pocket costs have delayed antimyeloma treatment, while 43% of patients have either partially filled a prescription for or discontinued antimyeloma therapy due to financial burden.³ Cost-related treatment delays and non-adherence are more pronounced among persons of color (POC).^3,5–7 Compared to White patients, POC are less likely to receive any systemic antimyeloma therapy⁶ and, among those who are treated, experience shorter periods of using novel, orally-administered medications.^5,7 Given that timely initiation and continued use of therapy are necessary for optimal clinical outcomes,⁸ identifying and evaluating policy solutions that address cost-related barriers to care are imperative.

The Medicare Part D low-income subsidy (LIS) program substantially reduces out-of-pocket costs for beneficiaries with limited incomes (e.g., <135% of the federal poverty level) and assets (e.g., ≤$9,470 for individuals).^2,4,9 For example, in 2021 a 28-day supply of lenalidomide – one of the most expensive first-line, orally-administered antimyeloma medications – cost only $9.20 for a full subsidy enrollee⁹ compared to an average of $3,000 for a non-subsidized enrollee.¹⁰ Prior research has suggested that LIS program participation improves the uptake of and short-term adherence to anticancer therapies;^11–13 however, the role of reduced out-of-pocket costs on narrowing racial/ethnic inequities and the continuous use of therapy in older adults with multiple myeloma is limited. Our objectives were to compare the initiation of and adherence to orally-administered antimyeloma therapy between full subsidy and non-subsidy enrollees and to assess the association between the receipt of full subsidies and racial/ethnic inequities in antimyeloma treatment use.

METHODS

Study Population

We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to identify beneficiaries who were aged 66 years or older with a primary diagnosis of multiple myeloma (SEER site recode 34000) between January 2007 and December 2015. Eligible patients were (1) continuously enrolled in fee-for-service Medicare Parts A and B in the 12 months prior to diagnosis; (2) covered by fee-for-service Medicare Parts A, B, and D at diagnosis; (3) not diagnosed at autopsy or death; (4) not eligible for Medicare benefits due to end-stage renal disease; and (5) not receiving Medicare Part D partial subsidies at diagnosis. We further restricted the cohort to patients who were non-Hispanic/Latinx White (herein referred to as White), non-Hispanic/Latinx Black or African American (herein referred to as Black), Hispanic/Latinx, or Asian or Pacific Islander (herein referred to as Asian),^7,14 and had no prior evidence of antimyeloma treatment use (Figure 1).

Figure 1.

Consort Diagram

Abbreviations: ESRD, end-stage renal disease

^a Consistent with prior inequities studies, patients who were American Indian or Alaska Native were excluded from analyses due to limited sample size (n=31).

^b Patients who received antimyeloma therapy ≥32 days prior to diagnosis were excluded from all analyses. The initiation date of patients who received therapy <32 days before diagnosis was re-coded as the diagnosis date for initiation analyses (n=30).

Measures

Treatment Initiation

We identified Medicare Part D covered medications indicated for or commonly used to treat multiple myeloma: thalidomide, lenalidomide, pomalidomide, ixazomib, panobinostat, melphalan, cyclophosphamide, and etoposide (Appendix Table 1). We evaluated initiation in two ways: (1) time from diagnosis to orally-administered therapy initiation in the full cohort (n=6,972) (Figure 1; cohort 1); and (2) the probability of starting antimyeloma treatment within 30, 60, and 90 days⁴ of diagnosis among patients continuously enrolled in a Medicare Part D stand-alone plan for ≥3 months after diagnosis (n=6,268) (Figure 1; cohort 2).

Treatment Adherence and Discontinuation

Adherence to and discontinuation of orally-administered antimyeloma therapy were assessed among beneficiaries who were continuously enrolled in a Medicare Part D stand-alone plan in the 6 months following treatment initiation (n=3,091) (Figure 1; cohort 3). We defined adherence using the proportion of days covered (PDC)¹⁵ and allowed for switching between orally-administered therapies (e.g., due to treatment intolerance, therapy nonresponse, or disease progression).¹⁶ Consistent with prior research and Pharmacy Quality Alliance thresholds,^15,16 patients were categorized as adherent to antimyeloma therapy if PDC ≥80%. Discontinuation was defined as a gap of ≥60 consecutive days following exhaustion of available drug supply.¹⁶ We separately evaluated time from orally-administered therapy initiation to discontinuation among patients enrolled in a Medicare Part D stand-alone plan at time of initiation (n=3,563) (Figure 1; cohort 4).

LIS Program Participation

LIS program participation in the month of diagnosis was identified in the Medicare Part D enrollment file and beneficiaries were categorized as either full subsidy (dual-eligible or deemed eligible for reduced copayments) or non-subsidy (not eligible for cost-sharing subsidy) enrollees.^4,11

Covariates

Covariates included age at diagnosis, sex, marital status, urbanicity, quarter and year of diagnosis, comorbidity score (measured in the 12 months prior to diagnosis with the Klabunde modification of the Charlson score),^11,13 clinical markers of symptomatic multiple myeloma (diagnoses of hypercalcemia, renal impairment, anemia, and bone loss or lesions),¹⁷ prior health service use (hospitalizations and emergency department visits in the 12 months prior to diagnosis), and socioeconomic status (SES) and SES-related factors (census tract-level median household income, poverty level, high school education, and English proficiency).

Statistical Analyses

We used separate Cox proportional hazards models to evaluate time to orally-administered antimyeloma therapy initiation and discontinuation. In the initiation model, we accounted for death as a competing risk^13,18 and censored patients at Medicare Part D stand-alone plan disenrollment. In the discontinuation model, beneficiaries were censored at hospice enrollment, Medicare Part D stand-alone plan disenrollment, or death (whichever came first). We tested the proportionality assumption using martingale and Schoenfeld residuals¹⁹ and by adding time-dependent variables (interaction between covariate and log-time) to each model.²⁰ We also used modified Poisson regression²¹ with robust error variance to estimate the likelihood of starting therapy within 30, 60, and 90 days of diagnosis and adherence to and discontinuation of treatment in the 180 days following initiation.

Propensity Score-Weighting

To assess the independent association between subsidies and antimyeloma treatment use, we used stabilized inverse probability of treatment weights to balance observed patient- and census tract-level factors between full subsidy and non-subsidy enrollees. Characteristics were considered balanced if absolute standardized differences were <10% (Appendix Tables 2 and 3).²² Factors that were imbalanced following propensity score-weighting were added as covariates to the regression models (i.e., doubly-robust).²³

Measuring Racial/Ethnic Inequities

Consistent with the Institute of Medicine’s definition of disparities, we used a multivariable (non-weighted) model to first assess the independent effect of race/ethnicity by only controlling for health status (age at diagnosis, sex, marital status, aforementioned clinical characteristics, and prior health service utilization).^24,25 We then adjusted for urbanicity and census tract-level SES and SES-related factors to determine if racial/ethnic differences in antimyeloma therapy use were attenuated.^24,25 Finally, we stratified the models by subsidy status to understand whether full subsidies modify inequities in antimyeloma treatment use.

Sensitivity Analyses

We conducted several sensitivity analyses to check the robustness of our findings. First, individuals who qualified for Medicare due to a disability may have health needs that influence antimyeloma therapy uptake and utilization; therefore, we restricted analyses to patients whose reason for entitlement was age. Second, to further account for cases of symptomatic multiple myeloma, we restricted time-to-initiation analyses to patients treated within 12 months of diagnosis.⁷ Third, we examined initiation of infused antimyeloma treatment (Appendix Table 1) as a negative control because out-of-pocket costs are expected to be low for both full subsidy and non-subsidy enrollees.¹¹ Fourth, since adherence and discontinuation are related measures, we evaluated orally-administered therapy adherence among patients who did not discontinue treatment.¹⁶ Fifth, to account for expected clinical use of antimyeloma therapy among beneficiaries receiving an autologous stem cell transplant, we measured adherence in the first 120 days following treatment initiation.¹⁶ Lastly, orally-administered antimyeloma medications have varied toxicity profiles that could influence continued use; therefore, we included initial therapy and days’ supply in the propensity score models used to assess adherence and discontinuation.

RESULTS

Study Population Characteristics

Among the 6,972 beneficiaries with multiple myeloma, approximately 30% were receiving full subsidies and 29% were POC (Table 1). Compared to non-subsidy enrollees, full subsidy enrollees were less likely to be White (38% vs. 85%) and married (31% vs. 57%), but more likely to have multiple comorbidities (49% vs. 32%) and live in areas with high rates of poverty (44% vs. 17%). Following propensity score-weighting, baseline characteristics were well-balanced between full subsidy and non-subsidy enrollees (Appendix Table 2).

Table 1.

Baseline Characteristics of Full Subsidy and Non-subsidy Enrollees with Multiple Myeloma^a

	Full Subsidy Enrollees (n=2,075)	Non-subsidy Enrollees (n=4,897)	P Value
Demographics
Race/ethnicity
Non-Hispanic/Latinx White	793 (38.22)	4,169 (85.13)	<0.0001
Non-Hispanic/Latinx Black or African American	638 (30.75)	437 (8.92)
Hispanic/Latinx	403 (19.42)	173 (3.53)
Asian or Pacific Islander	241 (11.61)	118 (2.41)
Age at diagnosis
<71	487 (23.47)	1,159 (23.67)	0.8418
71–75	515 (24.82)	1,240 (25.32)
76–81	533 (25.69)	1,208 (24.67)
≥82	540 (26.02)	1,290 (26.34)
Sex
Male	864 (41.64)	2,504 (51.13)	<0.0001
Marital statusb
Married	638 (30.75)	2,795 (57.08)	<0.0001
Not married	1,293 (62.31)	1,754 (35.82)
Other/unknown	144 (6.94)	348 (7.11)
Urbanicityc
Big metro	1,158 (55.81)	2,522 (51.50)	0.0022
Metro	554 (26.70)	1,465 (29.92)
Urban	118 (5.69)	330 (6.74)
Less urban	186 (8.96)	475 (9.70)
Rural	59 (2.84)	105 (2.14)
Clinical Characteristics
Year of diagnosis
2007	242 (11.66)	383 (7.82)	<0.0001
2008	200 (9.64)	448 (9.15)
2009	221 (10.65)	453 (9.25)
2010	256 (12.34)	457 (9.33)
2011	253 (12.19)	477 (9.74)
2012	249 (12.00)	540 (11.03)
2013	225 (10.84)	702 (14.34)
2014	241 (11.61)	697 (14.23)
2015	188 (9.06)	740 (15.11)
Quarter of diagnosis
Q1	571 (27.52)	1,288 (26.30)	0.6288
Q2	517 (24.92)	1,219 (24.89)
Q3	503 (24.24)	1,249 (25.51)
Q4	484 (23.33)	1,141 (23.30)
Comorbidity scored
0	600 (28.92)	2,253 (46.01)	<0.0001
1	459 (22.12)	1,089 (22.24)
≥2	1,016 (48.96)	1,555 (31.75)
CRAB criteriae
Hypercalcemia	462 (22.27)	1,019 (20.81)	0.1740
Renal impairment	1,217 (58.65)	2,297 (46.91)	<0.0001
Anemia	1,137 (54.80)	2,888 (58.97)	0.0012
Bone loss or erosion	398 (19.18)	1,015 (20.73)	0.1420
Prior Health Service Use f
ED visits	950 (45.78)	1,567 (32.00)	<0.0001
Hospitalizations	865 (41.69)	1,363 (27.83)	<0.0001
Census Tract Factors
Median income
<$40,164.00	889 (42.84)	854 (17.44)	<0.0001
$40,164.00-<$55,846.00	539 (25.98)	1,198 (24.46)
$55,846.00-<$78,904.50	404 (19.47)	1,345 (27.47)
≥$78,904.50	243 (11.71)	1,500 (30.63)
% Below poverty levelc
<5%	184 (8.87)	1,321 (26.98)	<0.0001
5%-<10%	331 (15.95)	1,393 (28.45)
10%-<20%	639 (30.80)	1,357 (27.71)
≥20%	921 (44.39)	826 (16.87)
% English non-proficiency
≤1.47%	812 (39.13)	2,682 (54.77)	<0.0001
>1.47%	1,263 (60.87)	2,215 (45.23)
% High school diploma
<18.77%	384 (18.51)	1,355 (27.67)	<0.0001
18.77%-<26.94%	575 (27.71)	1,165 (23.79)
26.94%-<35.44%	556 (26.80)	1,192 (24.34)
≥35.44%	560 (26.99)	1,185 (24.20)

Abbreviations: ED, emergency department; IPTW, inverse probability of treatment weights

^aThe table displays characteristics prior to propensity score-weighting. Following propensity score-weighting, all covariates had an absolute standardized difference <0.10, thus suggesting negligible imbalance between full subsidy and non-subsidy enrollees (Appendix Table 2).

^bNot married includes patients who were single (never married), separated, divorced, or widowed at time of diagnosis, while Other/unknown includes patients that were unmarried or had a domestic partner (same sex, opposite sex, or unregistered) or unknown status at time of diagnosis.

^cPatients with “Unknown” urbanicity (11 patients) and poverty level (17 patients) were combined with the largest categories: “Big metro” and “10%-<20%”.

^dComorbidities were measured in the 12 months prior to multiple myeloma diagnosis using the Klabunde modification of the Charlson score.

^eCRAB criteria were measured in the 12 months prior to and 6 months following multiple myeloma diagnosis using the methods described by Fiala et al.

^fHealth service use was measured in the 12 months prior to multiple myeloma diagnosis.

Treatment Initiation

A smaller proportion of full subsidy enrollees (43%) started orally-administered antimyeloma therapy any time after diagnosis compared to non-subsidy enrollees (54%) (Figure 2, Panel A). However, treatment uptake within 30, 60, and 90 days of diagnosis was similar between full subsidy and non-subsidy enrollees (Appendix Figure 1, Panels A-C). In propensity score-weighted models, receipt of full subsidies was not associated with earlier orally-administered treatment initiation or starting antimyeloma therapy in the 30, 60, and 90 days following diagnosis (Appendix Table 4).

Figure 2.

Unadjusted Proportion of Enrollees who Used Orally-Administered Antimyeloma Therapy

^a Panel A represents the proportion of 6,972 enrollees who initiated orally-administered antimyeloma treatment any time after diagnosis. Panels B and C represent the proportion of 3,091 enrollees who adhered to (proportion of days covered ≥80%) and discontinued (gap ≥60 days) orally-administered antimyeloma therapy in the 180 days after diagnosis, respectively.

When assessing uptake by race/ethnicity, a lower percentage of Black full subsidy and non-subsidy enrollees initiated orally-administered treatment any time and in the 90 days after diagnosis compared to their White, Hispanic/Latinx, and Asian counterparts (Figure 2, Panel A and Supplementary Figure 1, Panel C). In the health status-adjusted models, receipt of full subsidies did not appear to narrow inequities in therapy initiation. Among both full subsidy and non-subsidy enrollees, Black patients were less likely than White patients to experience earlier orally-administered treatment initiation (full subsidy: adjusted hazard ratio [aHR] 0.86, 95% confidence interval [CI] 0.73–1.02; non-subsidy: aHR 0.86, 95% CI 0.74–0.99) (Table 2).

Table 2.

Racial/Ethnic Inequities in Orally-administered Antimyeloma Treatment Initiation

	Time to Initiationa,b		30 Daysa		60 Daysa		90 Daysa
	Effect of Racec	SES-Adjustedd	Effect of Racec	SES-Adjustedd	Effect of Racec	SES-Adjustedd	Effect of Racec	SES-Adjustedd
All Enrollees
Non-Hispanic/Latinx White	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
Non-Hispanic/Latinx Black or African American	0.85 (0.76–0.94)	0.87 (0.77–0.97)	0.94 (0.73–1.20)	1.01 (0.76–1.33)	0.85 (0.74–0.98)	0.86 (0.73–1.00)	0.84 (0.74–0.95)	0.84 (0.74–0.96)
Hispanic/Latinx	0.94 (0.83–1.06)	0.98 (0.85–1.13)	0.79 (0.56–1.12)	0.86 (0.58–1.25)	0.98 (0.83–1.16)	1.04 (0.86–1.26)	0.96 (0.83–1.11)	0.99 (0.85–1.32)
Asian or Pacific Islander	1.10 (0.96–1.28)	1.15 (0.98–1.34)	1.17 (0.82–1.66)	1.19 (0.81–1.74)	1.13 (0.94–1.36)	1.18 (0.97–1.45)	1.10 (0.94–1.28)	1.12 (0.85–1.17)
Full Subsidy Enrollees
Non-Hispanic/Latinx White	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
Non-Hispanic/Latinx Black or African American	0.86 (0.73–1.02)	0.87 (0.72–1.04)	0.90 (0.60–1.33)	0.98 (0.64–1.49)	0.85 (0.68–1.06)	0.85 (0.67–1.07)	0.85 (0.70–1.02)	0.88 (0.72–1.07)
Hispanic/Latinx	0.96 (0.79–1.15)	1.05 (0.86–1.29)	0.70 (0.42–1.15)	0.84 (0.48–1.46)	0.94 (0.73–1.21)	1.02 (0.77–1.35)	0.88 (0.72–1.09)	0.99 (0.79–1.25)
Asian or Pacific Islander	1.15 (0.92–1.42)	1.18 (0.93–1.48)	1.06 (0.62–1.83)	1.26 (0.69–2.31)	1.17 (0.89–1.53)	1.28 (0.95–1.35)	1.10 (0.88–1.38)	1.23 (0.96–1.58)
Non-subsidy Enrollees
Non-Hispanic/Latinx White	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
Non-Hispanic/Latinx Black or African American	0.86 (0.74–0.99)	0.86 (0.74–1.00)	0.89 (0.62–1.29)	0.97 (0.66–1.43)	0.84 (0.68–1.03)	0.84 (0.68–1.03)	0.80 (0.67–0.96)	0.80 (0.67–0.96)
Hispanic/Latinx	1.03 (0.83–1.27)	1.03 (0.83–1.27)	0.94 (0.55–1.63)	1.01 (0.58–1.77)	1.14 (0.88–1.48)	1.19 (0.91–1.54)	1.11 (0.89–1.38)	1.14 (0.91–1.42)
Asian or Pacific Islander	1.11 (0.89–1.40)	1.13 (0.90–1.43)	1.28 (0.74–2.21)	1.27 (0.73–2.21)	1.02 (0.75–1.40)	1.05 (0.77–1.44)	0.98 (0.75–1.28)	0.99 (0.76–1.30)

Abbreviations: SES, socioeconomic status

^aHazard ratios and 95% confidence intervals are presented for time to initiation and risk ratios and 95% confidence intervals are presented for treatment started within 30, 60, and 90 days of diagnosis. 6,972 patients were included in the time to initiation analysis and 6,268 patients were included in the analysis of treatment started within 30, 60, and 90 days of diagnosis.

^bAll enrollees models and full subsidy enrollees models were stratified by hypercalcemia; and hypercalcemia, bone loss, and age at diagnosis, respectively, since the proportionality assumption was not satisfied for these variables.

^cIn accordance with the Institute of Medicine’s definition of disparities, we assessed the independent effect of race/ethnicity by only controlling for health status (age at diagnosis, sex, marital status, clinical characteristics, and prior health service use).

^dWe adjusted for urbanicity and census tract-level SES and SES-related factors (median household income, poverty level, high school education, and English proficiency) to determine if observed racial/ethnic differences in treatment initiation were attenuated.

Treatment Adherence and Discontinuation

Less than half of full subsidy (35%) and non-subsidy (41%) enrollees were adherent to orally-administered therapy (Figure 2, Panel B), but a larger proportion of full subsidy enrollees discontinued treatment compared to non-subsidy enrollees (40% vs. 33%) (Figure 2, Panel C). In weighted models, receipt of full subsidies was not associated with adherence to or discontinuation of antimyeloma treatment in the 180 days following initiation (Appendix Table 5). However, full subsidy enrollees had a 22% (aHR 1.22, 95% CI 1.08–1.38) increased likelihood of earlier therapy discontinuation relative to non-subsidy enrollees.

We observed low rates of adherence across all races/ethnicities (Figure 2, Panel B). For example, only 30% of Black full subsidy enrollees and 31% of Asian non-subsidy enrollees adhered to antimyeloma therapy. A larger percentage of White, Black, Hispanic/Latinx, and Asian full subsidy enrollees discontinued treatment relative to their non-subsidized counterparts, with the largest difference observed between Black full subsidy and non-subsidy enrollees (43% vs. 25%) (Figure 2, Panel C). In the health status-adjusted models, we did not observe statistically significant differences in orally-administered therapy adherence and discontinuation between White patients and Black, Hispanic/Latinx, and Asian patients who received full subsidies (Table 3). Compared to White non-subsidy enrollees, Black non-subsidy enrollees were 27% (adjusted risk ratio [aRR] 0.73, 95% CI 0.57–0.95) and 26% (aHR 0.74, 95% CI 0.56–0.98) less likely to discontinue antimyeloma therapy or experience earlier treatment discontinuation, respectively. Findings were similar when controlling for SES and SES-related factors.

Table 3.

Racial/Ethnic Inequities in Adherence to and Discontinuation of Orally-administered Antimyeloma Therapy

	Adherencea		Discontinuationa		Time to Discontinuationa,b
	Effect of Racec	SES-Adjustedd	Effect of Racec	SES-Adjustedd	Effect of Racec	SES-Adjustedd
All Enrollees
Non-Hispanic/Latinx White	Ref	Ref	Ref	Ref	Ref	Ref
Non-Hispanic/Latinx Black or African American	0.98 (0.85–1.13)	1.09 (0.94–1.27)	0.94 (0.81–1.09)	0.82 (0.70–0.97)	0.99 (0.84–1.17)	0.85 (0.71–1.03)
Hispanic/Latinx	1.12 (0.95–1.31)	1.22 (1.03–1.46)	1.01 (0.85–1.20)	0.94 (0.77–1.15)	1.05 (0.86–1.28)	0.90 (0.71–1.13)
Asian or Pacific Islander	0.87 (0.70–1.07)	0.90 (0.73–1.12)	0.99 (0.80–1.23)	0.94 (0.74–1.18)	1.03 (0.80–1.32)	0.92 (0.70–1.20)
Full Subsidy Enrollees
Non-Hispanic/Latinx White	Ref	Ref	Ref	Ref	Ref	Ref
Non-Hispanic/Latinx Black or African American	0.96 (0.73–1.25)	1.02 (0.77–1.34)	1.00 (0.80–1.24)	0.98 (0.78–1.23)	1.00 (0.77–1.29)	0.98 (0.75–1.28)
Hispanic/Latinx	1.14 (0.88–1.46)	1.13 (0.87–1.48)	0.95 (0.74–1.21)	1.01 (0.77–1.32)	0.86 (0.65–1.15)	0.91 (0.66–1.26)
Asian or Pacific Islander	0.95 (0.70–1.28)	0.87 (0.63–1.20)	0.96 (0.71–1.29)	1.01 (0.74–1.39)	0.81 (0.57–1.16)	0.88 (0.61–1.28)
Non-subsidy Enrollees
Non-Hispanic/Latinx White	Ref	Ref	Ref	Ref	Ref	Ref
Non-Hispanic/Latinx Black or African American	1.10 (0.92–1.30)	1.19 (0.99–1.42)	0.73 (0.57–0.95)	0.67 (0.51–0.88)	0.74 (0.56–0.98)	0.64 (0.48–0.86)
Hispanic/Latinx	1.14 (0.88–1.48)	1.19 (0.92–1.55)	1.02 (0.74–1.41)	1.03 (0.74–1.42)	1.14 (0.81–1.60)	1.13 (0.80–1.61)
Asian or Pacific Islander	0.78 (0.55–1.12)	0.78 (0.55–1.11)	0.88 (0.60–1.30)	0.95 (0.64–1.40)	0.97 (0.64–1.47)	1.05 (0.69–1.60)

Abbreviations: SES, socioeconomic status

^aRisk ratios and 95% confidence intervals are presented for adherence and discontinuation within 180 days of treatment initiation and hazard ratios and 95% confidence intervals are presented for time to discontinuation. 3,091 patients were included in the analysis of adherence and discontinuation within 180 days of treatment initiation and 3,563 patients were included in the analysis of time to discontinuation.

^bThe all enrollees independent effect of race and SES-adjusted models were stratified by marital status, bone loss, and age at diagnosis; and marital status, bone loss, age at diagnosis, and high school education, respectively, since the proportionality assumption was not satisfied for these variables. Similarly, the full subsidy enrollees and non-subsidy enrollees models were stratified by bone loss; and age at diagnosis, marital status, and year of diagnosis, respectively.

^cIn accordance with the Institute of Medicine’s definition of disparities, we assessed the independent effect of race/ethnicity by only controlling for health status (age at diagnosis, sex, marital status, clinical characteristics, and prior health service use).

^dWe adjusted for urbanicity and census tract-level SES and SES-related factors (median household income, poverty level, high school education, and English proficiency) to determine if observed racial/ethnic differences in treatment use were attenuated.

Sensitivity Analyses

Full subsidy enrollees were less likely than non-subsidy enrollees to experience earlier infused therapy initiation (aHR 0.81, 95% CI 0.75–0.88) or start infused treatment within 60 (aRR 0.84, 95% CI 0.73–0.98) and 90 (aRR 0.88, 95% CI 0.77–1.00) days of diagnosis (Appendix Table 6). Results of remaining sensitivity analyses were consistent with our primary findings and are not shown.

DISCUSSION

In this study comparing the use of orally-administered antimyeloma therapy between Medicare Part D full subsidy and non-subsidy enrollees, we found no statistically significant differences in earlier therapy initiation or rates of treatment adherence. In addition, reduced cost-sharing did not appear to minimize racial/ethnic inequities in multiple myeloma care. We observed inequities in the uptake of orally-administered therapy among both full subsidy and non-subsidy enrollees; however, no statistically significant differences in therapy adherence were observed by race/ethnicity and subsidy status.

One possible explanation for our findings and inconsistencies with previous studies^11,13,26 is that utilization management processes²⁷ and restricted distribution networks^27,28 likely contributed to therapy delays for both full subsidy and non-subsidy enrollees. In regard to the former, research has demonstrated median treatment delays of ≤20 days for initial prior authorization approval and an additional 30 days for an appeal to be filed and approved.^29,30 In terms of the latter, risk evaluation and mitigation strategy programs limit the number of specialty pharmacies allowed to dispense immunomodulatory agents (lenalidomide, thalidomide, pomalidomide),²⁸ which has resulted in therapy delays for approximately one-quarter of patients.²⁸ Although efforts to streamline processes and evaluate programs for barriers to care have been proposed,^28,31 payers and policymakers should consider permanent reforms to ensure timely access to life-extending antimyeloma therapies.

High out-of-pocket costs may have also limited access to orally-administered therapy for some non-subsidy enrollees. Evidence suggests that out-of-pocket costs >$2,000 are associated with abandonment of prescriptions for immunomodulatory agents.³² Although some patients may eventually fill a prescription (e.g., after obtaining financial support), others may choose to initiate infused therapy due to the generosity of coverage for outpatient medical services. Since most fee-for-service Medicare beneficiaries have supplemental insurance to aid with out-of-pocket expenses,³³ reduced cost-sharing may only partially explain why non-subsidy enrollees were more likely than full subsidy enrollees to initiate infused antimyeloma therapy. Potential reasons for the undertreatment of full subsidy enrollees include poor patient-provider communication (e.g., limited discussions regarding treatment options),³⁴ inadequate social support,³⁵ structural barriers (e.g., lack of reliable transportation, dearth of healthcare providers),^35,36 and patients’ beliefs and preferences (e.g., understanding of disease severity and treatment benefits or side-effects).^27,35,37

Common barriers to accessing antimyeloma therapy could also explain why full subsidy enrollees had a 22% higher probability of discontinuing orally-administered treatment; however, our findings indicate that reduced cost-sharing may not improve the continuous use of high-cost therapies. Studies have shown that out-of-pocket costs ≤$3 adversely impact the prolonged use of medications among low-income patients.¹² While full subsidy enrollees often pay $1 for a monthly supply of anticancer therapy,^26,38 approximately 1.2 million are exposed to greater cost-sharing because they are enrolled in Medicare Part D plans in which they pay a monthly premium.³⁹ Full subsidy enrollees could switch to plans that minimize cost-sharing,³⁹ yet many have a poor understanding of the Medicare Part D program⁴⁰ and thus, do not enroll in a plan that aligns with their health and financial needs. As the number of no-premium plans is expected to decrease by 24% in 2022,⁴¹ federal agencies should consider additional resources to aid full subsidy enrollees with plan selection to ensure that the LIS program is not inadvertently acting as a financial barrier to anticancer therapy use.

We also observed that Black full subsidy and non-subsidy enrollees had a lower likelihood of ever-initiating orally-administered therapy, which, to our knowledge, is not only novel, but also suggests that subsidies alone are insufficient to narrow racial/ethnic inequities in antimyeloma care. Research indicates that healthcare provider characteristics (e.g., demographics, implicit bias, training) independently influence quality of care, including the underprescribing of medication and timely receipt of aggressive therapies.^42,43 For example, implicit bias during patient-provider racially discordant interactions has been associated with limited patient-centered communication^43,44 and shared decision-making,^44,45 patient’s lack of confidence in and non-adherence with recommended treatment plans,⁴³ and patient’s overall perceptions of mistrust of and dissatisfaction with the healthcare system.^44,45 Given the low rates of treatment initiation^3,5 and high risk of excess mortality⁵ among Black patients with multiple myeloma, future studies should focus on the development of interventions that improve patient-provider communication and address healthcare providers’ biases.

Contrary to prior research,¹² we found that Black non-subsidy enrollees were less likely than their White counterparts to discontinue orally-administered treatment. White non-subsidy enrollees may have been prescribed a shorter duration of antimyeloma therapy (e.g., 3 to 4 cycles of induction therapy with lenalidomide) in preparation for an autologous stem cell transplant. Approximately 28% of older adults (aged ≥70 years) receive an autologous stem cell transplant,⁴⁶ yet White patients are undergoing transplantation at a greater frequency than Black patients.^5,6 Although it may appear that racial inequities in autologous stem cell transplantation are contributing to the continuous use of orally-administered therapy among Black non-subsidy enrollees, future research is needed to identify the underlying factors and the short- and long-term clinical outcomes associated with these inequities.

Limitations

This study had several limitations. First, causality could not be assessed in our observational study and residual confounding resulting from unobserved characteristics may not have been addressed by our statistical models. Second, we were not able to discern reasons for not starting, delaying, or stopping orally-administered antimyeloma therapy. Future research should assess healthcare providers’ and patients’ treatment preferences to identify barriers to and the root causes of inequities in therapy uptake and continued use. Third, we lacked data on the receipt of prescription assistance outside of the Medicare Part D program. Cost-sharing support could have provided enrollees with the financial resources to start and/or adhere to orally-administered therapy. Fourth, our analysis did not account for phases of the Medicare Part D benefit. Non-subsidy enrollees who reached catastrophic coverage likely had relatively low out-of-pocket costs that contributed to continued treatment use. Fifth, we were limited to census tract-level SES and SES-related factors and thus, may have misclassified individuals’ SES. Future studies should examine both patient- and area-level SES to better understand the associations between out-of-pocket costs, race/ethnicity, and orally-administered anticancer medication use.¹² Sixth, our analysis did not account for known barriers to health equity.^47,48 Future research should examine the role of structural racism (e.g., residential segregation, scientific racism) on access to and use of anticancer therapy.^47,48 Seventh, our analysis focused on fee-for-service beneficiaries, which may limit the generalizability of our findings to patients covered by Medicare Advantage plans.. Eighth, some beneficiaries may have remained untreated due to asymptomatic multiple myeloma;^49,50 however, a growing body of literature suggests that early intervention with orally-administered therapy may prevent progression to symptomatic disease and improve overall survival.^49,50 Ninth, PDC only measures prescription refills and we were not able to determine if patients actually ingested medication as prescribed. Lastly, although we did not account for hospitalizations, both adherent and non-adherent hospitalized patients experienced short duration of stays (median ≤3 days) that would not have meaningfully changed our measures of orally-administered treatment use.

CONCLUSION

Receipt of Medicare Part D full subsidies does not appear to improve the use of or reduce racial/ethnic inequities in the initiation of orally-administered antimyeloma therapy. Policymakers, healthcare providers, and researchers should focus on identifying the underlying causes of suboptimal treatment use and developing interventions to address known barriers to access. Together, these actions could improve the uptake and equitable use of high-cost antimyeloma therapy.

TAKE-AWAY POINTS:

• Medicare Part D low-income subsidies reduce cost-sharing and may increase the uptake and equitable use of high-cost antimyeloma medications.

• Receipt of full subsidies was not associated with the timely initiation of or improved adherence to orally-administered antimyeloma medications. Moreover, Black enrollees were less likely than White enrollees to ever-initiate antimyeloma therapy, regardless of subsidy status.

• Addressing known barriers to care (e.g., implicit bias, social determinants of health) could improve use of high-cost antimyeloma therapy and reduce racial/ethnic inequities in antimyeloma care.