Clinical Benefits and Commonly Reported Adverse Events and Their Associated Costs in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors in First-Line and Relapsed/Refractory Settings

Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase inhibitors (BTKis) approved for treatment of chronic lymphocytic leukemia (CLL). This study use data from package inserts, clinical trials and real-world evidence to evaluate the clinical benefits and commonly reported adverse events (AEs) to assess associated treatment-related and adverse event related (AE) costs of BTKis.

This study estimated the clinical outcomes and cost of BTKi treatment for first-line (1L) and relapsed/refractory (R/R) CLL using a semi-Markov simulation model while incorporating treatment-related care among patients in progression-free survival and post-progression health states as well as the overall survival, safety, and tolerability data from the US Medicare perspective. Treatment-related costs (reported as per treated patient per month [PTPPM]) included costs associated with routine maintenance and clinical care; AE-related costs were also reported over a 1-year and 5-year time horizon. AE PTPPM costs were applied over a 1-year time horizon due to inconsistent reporting at longer time points. Scenario analyses examined ibrutinib relative to acalabrutinib and zanubrutinib using head-to-head (H2H) clinical trials, ELEVATE-RR and ALPINE. A scenario analysis also examined the impact of ibrutinib dose reduction (DR).

AE costs among patients treated in an R/R setting, and as informed by H2H clinical trials and published cost estimates, were primarily driven by (in descending order by overall total proportion of AE-related costs, across both trials) neutropenia (32%), infection (24%), pneumonia (12%), thrombocytopenia (9%), anemia (8%), hypertension (6%), and atrial fibrillation (5%). H2H clinical trials among patients with R/R CLL continue to suggest that PTPPM AE-related costs are similar across BTKis; ELEVATE-RR (ibrutinib: $863 vs acalabrutinib: $822) and ALPINE (ibrutinib: $581 vs zanubrutinib: $570). Among modeled patients with 1L CLL, average total life-years over 1-year/5-year time horizons for ibrutinib, acalabrutinib, and zanubrutinib were 0.99/4.80, 0.99/4.68, and 0.99/4.65, respectively. Discounted treatment-related costs PTPPM were $48/$64, $46/$58, and $46/$60, and AE PTPPM costs were $520, $457, and $489, respectively. For modeled R/R CLL, average total life-years over 1-year/5-year time horizons for ibrutinib, acalabrutinib, and zanubrutinib were 0.96/4.08, 0.96/4.16, and 0.97/4.35, respectively. Treatment-related PTPPM costs were $87/$96, $90/$108, and $86/$93, and AE PPPM costs were $740, $706, and $570, respectively. Potential ibrutinib DR among eligible patients resulted in a drop in AE PTPPM costs to $499 averaged across all patients with 1L CLL treated with ibrutinib and AE PTPPM costs to $710 averaged across all patients with R/R CLL.

Figure 1. AEs in ELEVATE-RR and ALPINE For Patients With CLL
(A) ELEVATE-RR and (B) ALPINE.
Abbreviations: AE, adverse events; CLL, chronic lymphocytic leukemia.

Based on conservative estimates of clinical efficacy and base case assumptions, the results of this study indicate comparable clinical benefits and costs among different BTKis in 1L CLL. Furthermore, when considering potential dose reductions in eligible patients, the clinical benefits and treatment-related costs remain similar in R/R CLL. Additionally, conducting scenario analyses using recently published real-world evidence and clinical trials could potentially highlight the value of ibrutinib in relation to other BTKis.

Funding:

Research funding provided by AbbVie, Genentech, Janssen, and Novartis; travel/accommodations/expenses from AstraZeneca.

Disclosures:

S.C., H.L., and B.S. stated employment and stock or other ownership with AbbVie. P.M. and J.G. stated employment with Medical Decision Modeling Inc. K.A.R. stated consultancy with AbbVie, Acerta Pharma, AstraZeneca, BeiGene, Genentech, Innate Pharma, and Pharmacyclics LLC, an AbbVie company.

Authors:

Samuel Crawford, PhD¹;Huimin Li, MA¹; Bhavini Srivastava, MSc¹; Pam Martin, PhD²; James Gahn²; Kerry A. Rogers, MD³

Affiliations:

¹AbbVie, North Chicago, IL

₂Medical Decision Modeling Inc., Indianapolis, IN

₃The Ohio State University, Columbus, OH