Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis

Abstract

Purpose: The goal of this study was to estimate the relative efficacy of acalabrutinib (monotherapy and in combination with obinutuzumab) compared with standard frontline treatments for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, through a network meta-analysis (NMA). Methods: The efficacy of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) was compared to bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy and venetoclax + obinutuzumab using data from eight randomized controlled trials (RCTs). Relevant RCTs were identified using a systematic literature review. Two evidence networks were constructed: Network A, composed solely of RCTs that met the inclusion criteria; and Network B, composed of 7 RCTs and a published crosstrial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE. Bayesian NMAs were conducted on progression-free survival (PFS) and overall survival (OS) endpoints; results were reported by using hazard ratios (HRs) and 95% credible intervals (CrIs). HRs were considered significant if their CrIs did not cross 1. Treatments were ranked by using the surface under the cumulative

Cost-effectiveness of a 12-month fixed-duration venetoclax treatment in combination with obinutuzumab in first-line, unfit chronic lymphocytic leukemia in the United States

“…The model, although comprehensive, has some limitations. The HRs from our NMA are a key determinant of the external comparators' outcomes in the current analysis; however, other recently published NMAs have noted similar findings, 53,54 that is, that Acala and Acala + G achieve better PFS outcomes than VenG, thereby supporting the findings of our NMA (although it should be noted that the NMAs are not strictly comparable, since our NMA included only studies with unfit, previously untreated CLL populations). Further, since it is currently unknown whether patients who achieve remission after VenG but subsequently relapse benefit from repeat treatment with VenG, the current model does not consider the costs of VenG retreatment.…”

Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis

“…Overall, 138 records were retrieved: 13 fully published MAs reported PFS or OS ( Table 1 and Table 2 ) [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and 10 MAs reported safety outcomes ( Table 3 ) [ 8 , 9 , 11 , 15 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies

“…Because of its higher biochemical and cellular selectivity, acalabrutinib has an improved safety profile and exhibits a high efficacy in ibrutinib-intolerant CLL patients (6,11,12,(183)(184)(185)(186)(187). Despite its improved specificity and toxicity profile, common adverse effects of acalabrutinib have also been reported, including headache, diarrhea, fatigue, myalgias, cough, neutropenia, nausea, skin rash and infection (181,186,(188)(189)(190)(191) (Table 2).…”