Treatment sequence of lenalidomide and hypomethylating agents and the impact on clinical outcomes for patients with myelodysplastic syndromes

Figures & data

Table 1. Patient selection criteria.

Inclusion criteria	Exclusion criteria
≥18 years of age	Diagnosis of a second primary malignancy or receiving active treatment for a malignancy other than MDS during the study time frame
Diagnosis of MDS^a (ICD-9: 238.72–238.75 and ICD-10: D46)	Participation in a current clinical trial
Treated with either: HMA-LEN OR LEN-HMA
≥2 claims of 1L and ≥1 claim of 2L
≥6 months of follow-up post-first-line therapy initiation

1L: first-line therapy; 2L: second-line therapy; HMA: hypomethylating agent; LEN: lenalidomide; MDS: myelodysplastic syndromes.

^aThe ICD-9: 238.72 code is used for claims with a date of service on or before 30 September 2015. The ICD-10: D46 code is used for claims with a date of service on or before 1 October 2017.

Table 2. Patient attrition.

Inclusion criteria	Patients
	N		%
Patients with ≥1 claim with a diagnosis of MDS	6,009		100
Patients with ≥1 claim for LEN or HMA	530		8.8
	LEN-HMA		HMA-LEN
	N	%	N	%
Patients treated with either LEN-HMA or HMA-LEN	159	30.0	138	26.0
Patients ≥18 years old on index date^a	159	30.0	138	26.0
Patients with ≥2 claims of 1L (HMA or LEN)	135	25.5	135	25.5
Patients not participating in a clinical trial	122	23.0	122	23.0
Patients with ≥6 months of follow-up post 1L initiation	96	18.1	89	16.8

1L: first-line therapy; HMA: hypomethylating agent; LEN: lenalidomide; MDS: myelodysplastic syndromes.

^aIndex date is set at the earliest claim for LEN or HMA (azacitidine and decitabine).

Table 3. Patient demographic characteristics at baseline and clinical characteristics in the 6 months prior to the initiation of first-line therapy.

Characteristics	LEN-HMA (n = 96)	HMA-LEN (n = 89)	p
Gender, n (%)			.060
Male	54 (56.3)	62 (69.7)
Female	42 (43.7)	27 (30.3)
Mean age at 1L LEN or HMA, years (SD)	73.8 (8.0)	72.5 (8.9)	.288
Median age at 1L LEN or HMA, years	74.0	74.0
Payer type, n (%)			.707
Commercial	12 (12.5)	12 (13.5)
Medicaid	4 (4.2)	6 (6.7)
Medicare	73 (76.0)	68 (76.4)
Missing	6 (6.3)	2 (2.2)
Multiple	1 (1.0)	1 (1.1)
US region, n (%)			.020
Northeast	36 (37.5)	27 (30.3)
South	17 (17.7)	17 (19.1)
Midwest	20 (20.8)	16 (18.0)
West	13 (13.5)	27 (30.3)
Missing	10 (10.4)	2 (2.2)
SMMRS category, n (%)			.161
Low	0 (0.0)	1 (1.1)
Intermediate-1	82 (85.4)	67 (75.3)
Intermediate-2	14 (14.6)	21 (23.6)
High	0 (0.0)	0 (0.0)
Cytopenias, n (%)			.005
Anemia + neutropenia	13 (13.5)	17 (19.1)
Anemia + thrombocytopenia	12 (12.5)	13 (14.6)
Anemia + neutropenia + thrombocytopenia	12 (12.5)	26 (29.2)
CCI, mean (SD, median)	2.3 (2.4, 2.0)	2.9 (2.7, 2.0)	.098

1L: first-line therapy; CCI: Charlson Comorbidity Index; HMA: hypomethylating agent; LEN: lenalidomide; MDS: myelodysplastic syndromes; SD: standard deviation; SMMRS: SEER-Medicare MDS Risk Score.

Figure 1. Time to discontinuation. Median (95% CI) time to disenrollment, months: 19.0 (95% CI: 15.8–NR) among HMA-LEN patients and 29.0 (95% CI: 24.9–NR) among LEN-HMA patients (29.0 vs. 19.0 months; log-rank p = 009). LEN-HMA patients had a lower adjusted risk of discontinuation (HR: 0.52; 95% CI: 0.29–0.91; p=.023). 1L: first-line therapy; CI: confidence interval; HMA: hypomethylating agent; HR: hazard ratio; LEN: lenalidomide; NR: not reached.

Figure 2. Approximate median OS using time to insurance disenrollment. Median (95% CI) time to disenrollment, months: 16.1 (95% CI: 13.6–18.9) among HMA-LEN patients and 22.4 (95% CI: 19.5–27.7) among LEN-HMA patients (22.4 vs. 16.1 months; log-rank p<.001). LEN-HMA patients had a lower adjusted risk of disenrollment (HR: 0.64; 95% CI: 0.44–0.92; p=.017). 1L: first-line therapy; CI: confidence interval; HMA: hypomethylating agent; HR: hazard ratio; LEN: lenalidomide; OS: overall survival.

Table 4. Estimated yearly survival rate as approximated by annual insurance disenrollment rates.

Continuous enrollment, years	LEN-HMA, % (n = 96)	HMA-LEN, % (n = 89)
1	77.0	72.9
2	43.6	24.0
3	29.4	9.6
4	19.3	4.3
5	3.9	0.0

HMA: hypomethylating agent; LEN: lenalidomide.