Time to Next Treatment in Patients with Chronic Lymphocytic Leukemia Initiating First-Line Ibrutinib or Acalabrutinib

Figures & data

Figure 1. Study design.

1L: First-line; 2L: Second-line.

Figure 2. Identification of CLL/SLL patients treated with 1L ibrutinib or acalabrutinib.

¹The beginning of data availability is 01/01/2016. The end of data availability is the earlier of date of death or 04/30/2022. For patients without a date of death, 04/30/2022 is used as the end of data availability.

²ICD-10 CM code; N18.6.

³ICD-10 CM codes: C81-C82, C83.1-C83.7, C84, C85.2, C86, C88, C90, C91.0, C91.2-C91.6, C91.A, C92-C93, C94.0-C94.4, C95.0 and C96.

⁴Patients may use both acalabrutinib and ibrutinib. As such, the cohorts are not mutually exclusive at this step of the patient selection.

1L: First-line; CLL/SLL: Chronic lymphocytic leukemia/small lymphocytic lymphoma; ICD-10 CM: International Classification of Diseases, Tenth Revision, Clinical Modification.

Table 1. Baseline characteristics evaluated during the 12-month baseline period.

	Ibrutinib (n = 710)	Acalabrutinib (n = 373)	p-value ^†
Demographics ^§
Age at index date, mean ± SD (median)	71.5 ± 10.4 (73.0)	72.4 ± 9.8 (72.0)	0.159
Female, n (%)	273 (38.5)	143 (38.3)	0.971
Year of index date, n (%)
2019	45 (6.3)	7 (1.9)	0.001 ^‡
2020	408 (57.5)	119 (31.9)	<0.001 ^‡
2021	217 (30.6)	200 (53.6)	<0.001 ^‡
2022	40 (5.6)	47 (12.6)	<0.001 ^‡
Insurance coverage ^¶ , n (%)
Medicare	196 (27.6)	104 (27.9)	0.923
Managed care	61 (8.6)	34 (9.1)	0.772
Medicaid	15 (2.1)	0 (0.0)	0.005 ^‡
Other	252 (35.5)	137 (36.7)	0.687
Unknown	186 (26.2)	98 (26.3)	0.978
USA region, n (%)
South	213 (30.0)	138 (37.0)	0.019 ^‡
West	212 (29.9)	118 (31.6)	0.546
Midwest	188 (26.5)	86 (23.1)	0.218
Northeast	21 (3.0)	9 (2.4)	0.604
Unknown	76 (10.7)	22 (5.9)	0.009 ^‡
Race, n (%)
White	320 (45.1)	150 (40.2)	0.125
Black	25 (3.5)	19 (5.1)	0.213
Asian	13 (1.8)	7 (1.9)	0.958
Other	352 (49.6)	197 (52.8)	0.311
Clinical characteristics ^#
Quan-CCI, ^††  mean ± SD (median)	3.1 ± 1.7 (2.0)	3.0 ± 1.7 (2.0)	0.597
Chronic pulmonary disease, (n %)	94 (13.2)	32 (8.6)	0.023 ^‡
Peripheral vascular disease, (n %)	54 (7.6)	15 (4.0)	0.022 ^‡
Patients with pre-existing cardiovascular comorbidities, n (%)
Hypertension	294 (41.4)	120 (32.2)	0.003 ^‡
Atrial fibrillation	50 (7.0)	37 (9.9)	0.098
Metastatic cancer, n (%)	17 (2.4)	17 (4.6)	0.052
Use of corticosteroids, n (%)	103 (14.5)	75 (20.1)	0.018 ^‡
Use of antiplatelets, n (%)	50 (7.0)	13 (3.5)	0.017 ^‡

† p-values were calculated using t-tests for continuous variables and chi-square tests for categorical variables.

‡ indicates p-value < 0.05.

§ Demographic characteristics were evaluated on the date of treatment initiation.

¶ Insurance coverage type was identified by selecting the payer record closest to the index date.

# Evaluated in the up to 12-month baseline period, excluding the date of treatment initiation.

†† Reference: [74].

1L: First-line; Quan-CCI: Quan-Charlson comorbidity index; SD: Standard deviation.

Table 2. Treatment regimen received following 1L ibrutinib or acalabrutinib.

	Ibrutinib n = 710		Acalabrutinib n = 373
	N (%)	Time to initiation of next treatment, months, mean ± SD (median)	N (%)	Time to initiation of next treatment, months, mean ± SD (median)
Patients with a next treatment	42 (5.9)	9.2 ± 7.6 (6.8)	28 (7.5)	6.2 ± 4.6 (4.60
Treatment regimen received
Venetoclax	25 (59.5)	10.2 ± 8.2 (7.20)	14 (50.0)	4.8 ± 4.4 (2.8)
Obinutuzumab	1 (2.4)	1.4	3 (10.7)	4.6 ± 3.9 (3.4)
Rituximab	2 (4.8)	6.4 ± 6.4 (6.4)	0	–
Chlorambucil	2 (4.8)	4.3 ± 4.6 (4.3)	1 (3.6)	1.0
Lenalidomide	3 (7.1)	13.0 ± 5.4 (16.1)	0	–
Bendamustine + Rituximab	4 (9.5)	2.9 ± 0.8 (2.8)	0	–
Venetoclax + Obinutuzumab	0	–	3 (10.7)	8.7 ± 3.6 (8.9)
Venetoclax + Idelalisib	1 (2.4)	6.9	0	–
Venetoclax + Chlorambucil + Rituximab	0	–	1 (3.6)	3.3
BTKi + Venetoclax	3 (7.1)	15.5 ± 8.0 (11.7)	5 (17.9)	9.5 ± 3.3 (8.6)
BTKi + Obinutuzumab	0	–	1 (3.6)	14.5
BTKi + Lenalidomide	1 (2.4)	3.9	0	–

1L: First-line; BTKi: Bruton’s tyrosine kinase inhibitor; SD: Standard deviation.

Figure 3. Comparison of TTNT between 1L ibrutinib and 1L acalabrutinib.

*Indicates p-value < 0.05.

1L: First-line; HR: Hazard ratio; Pts: Patients; TTNT: Time to next treatment.

Table 3. Sensitivity analyses for the comparison of TTNT between 1L ibrutinib and 1L acalabrutinib ^† .

	Patients who switched to another regimen, n (%)		Adjusted Hazard Ratio ^‡ ^, ^¶ (95% CI)	p-value ^‡ ^, ^¶
	Ibrutinib (n = 710)	Acalabrutinib (n = 373)
Original results: Censoring patients with anti-CD20 or venetoclax add-on within 180 days	42 (5.9)	28 (7.5)	1.89 (1.12, 3.13)	0.016 ^§
Sensitivity analysis #1: Censoring patients with anti-CD20 add-on at any time	42 (5.9)	27 (7.2)	1.82 (1.08, 3.03)	0.025 ^§
Sensitivity analysis #2: Considering patients with an anti-CD20 add-on at any time as a next treatment	46 (6.5)	44 (11.8)	2.33 (1.49, 3.57)	<0.001 ^§
Sensitivity analysis #3: Considering patients with an anti-CD20 or venetoclax add-on at any time as a next treatment	56 (7.9)	52 (13.9)	2.22 (1.47, 3.33)	<0.001 ^§
Sensitivity analysis #4: Excluding patients with a within-class BTKi switch (sample size: N=663 for ibrutinib and N=369 for acalabrutinib)	42 (6.3)	28 (7.6)	1.82 (1.09; 3.03)	0.023 ^§

† Patients were considered as having the event if they initiate a subsequent regimen. TTNT was defined as the time from the index date to the earlier of initiation of a subsequent regimen or the last day of supply of ibrutinib or acalabrutinib. Patients not using a subsequent regimen are censored at the date of death or the end of data available. In all analyses, patients with an observed within-class BTKi switch (i.e., from ibrutinib to acalabrutinib or vice versa) were censored at the date of switch.

‡ Hazard ratios and their associated 95% CIs and p-values were estimated using weighted Cox proportional hazard models. A hazard ratio >1 indicates that patients treated with acalabrutinib had a higher risk of switching to another regimen than patients treated with ibrutinib.

§ Indicates p-value < 0.05.

¶ Models were also adjusted with the following variables: age, gender, region, race, year of index date, Quan-CCI, chronic pulmonary disease, peripheral vascular disease, hypertension, atrial fibrillation, metastatic cancer, use of corticosteroids and use of antiplatelets.

BTKi: Bruton’s tyrosine kinase inhibitor; Quan-CCI: Quan-Charlson comorbidity index; TTNT: Time to next treatment.

Quan H , Li B , Couris CM et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am. J. Epidemiol. 173(6), 676–682 (2011).

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Data Sharing Statement

The data that support the findings of this study are available from Acentrus, but restrictions apply to the availability of these data, which were used pursuant to a data use agreement. The data are available through requests made directly to Acentrus, subject to Acentrus’s requirements for data access.