Cost-Effectiveness Analyses of Ibrutinib vs Acalabrutinib vs Zanubrutinib as First-line Treatment in Patients With Chronic Lymphocytic Leukemia
When compared to chemoimmunotherapy, Bruton’s tyrosine kinase inhibitors (BTKis) have significantly improved progression-free survival (PFS) and overall survival (OS) outcomes in the front-line setting of chronic lymphocytic leukemia (CLL).
“Cost-effectiveness analyses of first-line ibrutinib versus acalabrutinib versus zanubrutinib followed by second-line venetoclax plus rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients,” a network meta-analysis of three BTKis in terms of PFS in support of cost-effectiveness analysis from the US payer perspective conducted by Neda Alrawashdh, PharmD, and colleagues was presented at the 64th American Society of Hematology Annual Meeting and Exposition. The researchers focused on the cost-effectiveness of first-line (1L) ibrutinib (IBR) vs acalabrutinib (ACA) vs zanubrutinib (ZAN), followed by second-line (2L) venetoclax plus rituximab (VR) in previously untreated patients with chronic lymphocytic leukemia (CLL).
The network meta-analysis consisted of five trials (Woyach 2018, Burger 2015, Sharman 2020, Tam 2021, and Goede 2014) on the PFS hazard ratios (HR) of the three BTKis.
A five-state Markov model was used to capture the disease and clinical pathway for patients with CLL over a 10-year period: progression-free (PF) on first-line (1L) treatment [PF1]; progression before initiating second-line (2L) treatment [P1]; PF on 2L treatment [PF2]; progression after 2L treatment [P2]; and death. Venetoclax + rituximab (VR) was considered the 2L treatment with PF2, P2, and death in 2L extracted from Seymour 2018.
All BTKis were considered to have the same OS and time to next treatment after first progression. Wholesale acquisition costs of the regimens, adverse event management, and disease progression were incorporated into the appropriate health states. Utilities of PF1 (0.799), P1 (0.66), PF2 (0.55), and P2 (0.42) were obtained from literature, and an annual discount rate of 3.0% was applied. Life years (LY), quality adjusted LY (QALY), and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were estimated, and cost-effectiveness acceptability curves (CEAC) were obtained.
When compared to IBR, ACA (HR = 0.54; 95% CI = 0.41-0.72) was associated with a statistically significant lower HR of progression or death; however, ZAN was not (HR = 1.03; 95% CI = 0.80-1.34).
At the 10-year mark, 77% of ACA patients were in PF1 and 9% in PF2, compared to 49% and 28% of ZAN patients, and 50% and 27% of IBR patients. Total costs of IBR treatment were higher by $104,331 than ACA and $350,340 higher than ZAN; with ACA being higher by $246,009 than ZAN.
Survival was estimated to be 6.83 LYs for IBR, 7.02 LYs for ACA (+0.19), and 6.82 LYs for ZAN (–0.01). QALYs were estimated to be 5.00 for IBR, 5.46 for ACA (+0.46), and 5.09 for ZAN (+0.09).
The statistically nonsignificant survival benefit, the 0.01 LY lost but 0.09 QALY gained (QALYg), and the lower cost of ZAN over IBR yielded an ICER of $35,034,000/LY gained (LYg) and a negative (cost-saving) ICUR of $3,892,666/QALYg.
“Acalubrutinib benefit comes at a lower cost than ibrutinib, which resulted in cost-saving ICUR and ICER, but at higher costs than zanubrutinib, which resulted in an ICUR of $500,000 per QALY gain,” Dr Alrawashdh presented.
QALYg were 5.25 for ACA, 4.40 for ZAN, and 4.34 for IBR in a scenario analysis for the PF1 state only. Considering cost differentials of –$69,138 for ACA and –$352,297 for ZAN relative to IBR, the corresponding ICURs were –$75,975/QALYg and –$5,871,617/QALYg, respectively.
According to the researchers, over the course of 1L treatment with a BTKi followed by 2L treatment with VR, ACA in 1L is associated with greater reductions in progression risk or death compared to IBR and ZAN over 10 years.
“The NMA shows that acalabrutinib is associated with greater reduction in the risk of death or progression than ibrutinib or zanubrutinib,” concluded Dr Alrawashdh. “This resulted in more gain in terms of life year and QALY when compared with ibrutinib or zanubrutinib in the cost effectiveness analysis.”
Alrawashdh N, McBride A, Abraham I. Cost-Effectiveness Analyses of First Line Ibrutinib Versus Acalabrutinib Versus Zanubrutinib Followed By Second Line Venetoclax Plus Rituximab in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Patients. Presented at the 64th ASH Annual Meeting and Exposition. December 10-13, 2022. Abstract 889.
