Cost-effectiveness of acalabrutinib regimens in treatment-naïve chronic lymphocytic leukemia in the United States

Figures & data

Figure 1. Diagram of the three-state semi-Markov model structure.

TP1 represents the probability of the patient transitioning from PF to PD. TP2 represents the probability of the patient transitioning from PF to Death. TP3 represents the probability of the patient transitioning from PD to Death. Transition probabilities are described within the Methods section (Clinical data). Not shown are tunnel states for each possible transition during each cycle to model time-dependent transitions. PD, progressed disease; PF, progression-free; TP, transition probability.

Figure 2. Parametric models overlaying the TTP Kaplan–Meier data for all comparators.

Parametric distributions were selected based on the lowest AIC/BIC values along with clinical plausibility. AIC, Akaike information criterion; BIC, Bayesian information criterion; KM, Kaplan–Meier; TTP, time to progression.

Figure 3. Parametric models overlaying the TTDeath Kaplan–Meier data for all comparators.

Parametric distributions were selected based on the lowest AIC/BIC values along with clinical plausibility. Note: AIC, Akaike information criterion; BIC, Bayesian information criterion; KM, Kaplan–Meier; TTDeath, time to death.

Table 1. Model parameters and goodness-of-fit indicators for the distributions of TTP, TTDeath, and PPS curves.

	Distribution parameter (95% CI)
	Exponential	Lognormal	AIC/BIC
TTP
Acalabrutinib monotherapy	0.0030818 (0.0020292–0.0046804)		300.42/303.61
Acalabrutinib + obinutuzumab	0.0015983 (0.00090767–0.0028143)		180.53/183.72
Chlorambucil + obinutuzumab		Mean log: 3.4174 (3.286–3.5488) SD log: 0.76849 (0.66477–0.88838)	949.16/955.51
TTDeath
Acalabrutinib monotherapy	0.0019612 (0.0011615–0.0033113)		204.56/207.75
Acalabrutinib + obinutuzumab	0.0011987 (0.0006237–0.0023038)		141.08/144.26
Chlorambucil + obinutuzumab	0.0026105 (0.0014825–0.0045967)		168.76/171.93
PPS
Acalabrutinib monotherapy
Acalabrutinib + obinutuzumab	0.0046614 (0.0031967–0.0067972)		345.90/349.44
Chlorambucil + obinutuzumab	0.0092236 (0.0065905–0.012909)		388.65/391.89

AIC, Akaike information criterion; BIC, Bayesian information criterion; PPS, postprogression survival; TTDeath, time to death; TTP, time to treatment progression.

Table 2. Parameters implemented in the model base case analysis.

Parameter	All	A	A + O	C + O	Reference	Comments
Health state utility values
PF	0.748				NICE TA 561 [16]
PD	0.600				NICE TA 561 [16]
Unit costs for drugs in first-line regimens
Acquisition costs, $
Acalabrutinib
Package price	14,064.00				Micromedex Red Book® [17]	WAC price; lowest cost/mg pack used
Discounted price	13,360.80	X	X			Expected 5% manufacturer discount applied; based on ICER recommendations [11]
Obinutuzumab
Package price	6848.75				Micromedex Red Book [17]	WAC price; lowest cost/mg pack used
Discounted price	6506.31		X	X		Expected 5% manufacturer discount applied; based on ICER recommendations [11]
Chlorambucil
Package price	662.93				Micromedex Red Book [17]	WAC price; lowest cost/mg pack used
Discounted price	629.78			X		Expected 5% manufacturer discount applied; based on ICER recommendations [11]
Obinutuzumab administration costs	Dependent on # of cycles	0	Cycle 1: N/A Cycle 2: 1095.60 Cycle>2: 273.90	Cycle 1: 1095.60 Cycle≥2: 273.90	CMS HCPCS 96,413 and 96,415 [18]
Treatment-related AE incidence rates, %
ALT/AST increased		0.6	4.5	3.0	ELEVATE-TN
Anemia		7.4	6.4	7.7	ELEVATE-TN
Atrial Fibrillation		1.1	0.6	0.0	ELEVATE-TN
Bleeding		2.8	1.7	0.0	ELEVATE-TN
Chest pain		0.0	1.1	0.0	ELEVATE-TN
Diarrhea		0.6	5.1	1.8	ELEVATE-TN
Febrile neutropenia		1.1	1.7	5.3	ELEVATE-TN
Infusion-related reaction		0.0	2.8	5.9	ELEVATE-TN
Leukocytosis		1.1	0.6	0.0	ELEVATE-TN
Neutropenia		11.2	30.9	41.4	ELEVATE-TN
Neutrophil count decreased		0.0	1.1	3.0	ELEVATE-TN
Thrombocytopenia		3.4	8.4	11.2	ELEVATE-TN
Tumor lysis syndrome		0.0	1.7	8.9	ELEVATE-TN
Dyspnea		2.8	1.1	1.8	ELEVATE-TN
Fatigue		1.1	2.2	1.2	ELEVATE-TN
Infections and infestations		15.3	22.1	8.3	ELEVATE-TN
Hypertension		2.8	4.1	3.6	ELEVATE-TN
Rash		0.0	0.6	0.6	ELEVATE-TN
Secondary primary malignancies		3.4	6.4	1.8	ELEVATE-TN
Syncope		1.7	3.9	0.6	ELEVATE-TN
Back pain		3.4	0.6	0.6	ELEVATE-TN

The model accounts for the impact of all clinically relevant treatment-related grade ≥3 AEs that occurred in any arm at the 47-month data cutoff. Incidence rates and associated costs and utility decrements are applied in the first cycle of the model. Costs ($) represent 2021 US dollars. ‘X’ indicates to which treatment regimens an acquisition cost applied.

A, acalabrutinib; AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; C, chlorambucil; CMS HCPCS, Centers for Medicare & Medicaid Services Healthcare Common Procedure Coding System; ICER, incremental cost-effectiveness ratio; NICE TA, (UK) National Institute for Health and Care Excellence technology appraisal; O, obinutuzumab; PD, progressed disease; PF, progression-free; WAC, wholesale acquisition cost.

Table 3. Incremental cost-effectiveness results from the base case analysis.

Interventions	Incremental cost ($)	Incremental QALYs	ICER ($ cost/QALY)
Acalabrutinib	206,329	2.52	81,960
Acalabrutinib + obinutuzumab	423,747	2.79	152,153

Results represent the differences between the interventions and the comparator (chlorambucil + obinutuzumab) in terms of additional costs and benefits. Incremental results are calculated as intervention values minus comparator values. The ICER is calculated as incremental cost divided by incremental QALYs, and represents the additional cost necessary to gain 1 additional QALY using the intervention vs the comparator treatment regimen. Costs ($) represent 2021 US dollars.

ICER, incremental cost-effectiveness ratio; LY, life-year; QALY, quality-adjusted life-year.

Figure 4. Deterministic sensitivity analyses: Tornado diagrams showing results for acalabrutinib monotherapy (a) and acalabrutinib + obinutuzumab (b) vs chlorambucil + obinutuzumab.

Costs ($) represent 2021 US dollars. Low and high values for each parameter were based on their 95% confidence intervals or ±20% of their base case values when 95% confidence intervals were unavailable.

Figure 5. Probabilistic sensitivity analysis results for acalabrutinib monotherapy vs chlorambucil + obinutuzumab: Cost-effectiveness plane (a) and cost-effectiveness acceptability curves (b).

Costs ($) represent 2021 US dollars. QALY, quality-adjusted life-year.

Figure 6. Probabilistic sensitivity analysis results for acalabrutinib + obinutuzumab vs chlorambucil + obinutuzumab: Cost-effectiveness plane (a) and cost-effectiveness acceptability curves (b).

Costs ($) represent 2021 US dollars. QALY, quality-adjusted life-year.

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