A matching-adjusted indirect comparison (MAIC) of the efficacy and safety of acalabrutinib (acala) versus zanubrutinib (zanu) in relapsed or refractory chronic lymphocytic leukemia (RR CLL).

Medientyp: E-Artikel

Titel: A matching-adjusted indirect comparison (MAIC) of the efficacy and safety of acalabrutinib (acala) versus zanubrutinib (zanu) in relapsed or refractory chronic lymphocytic leukemia (RR CLL)

Beteiligte: Kittai, Adam; Skarbnik, Alan; Miranda, Miguel; Yong, Alan SM; Roos, Jack; Hettle, Robert; Palazuelos-Munoz, Sarah; Shetty, Vikram; Ghia, Paolo

Erschienen: American Society of Clinical Oncology (ASCO), 2023

Sprache: Englisch

DOI: 10.1200/jco.2023.41.16_suppl.7540

ISSN: 0732-183X; 1527-7755

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Beschreibung: 7540 Background: The BTKi ibrutinib is the standard of care in RR CLL and was compared in head-to-head randomized clinical trials (RCTs) with second-generation BTKis: acala in ELEVATE-RR and zanu in ALPINE. However, major differences in these RCT's populations prevents comparison of acala and zanu. Acala was also assessed in the ASCEND RCT, which had a similar population to ALPINE but a different comparator. Thus, we used unanchored MAIC to compare the efficacy and safety of acala vs zanu using individual patient data (IPD) from ASCEND and published aggregate data from ALPINE. Methods: In the unanchored MAIC, acala IPD from ASCEND were weighted to match zanu baseline data from ALPINE. This reduced between-study differences in variables that were prognostic/effect-modifying of progression-free survival (PFS) in an exploratory multivariate cox regression analysis of ASCEND. These included sex, ECOG PS, bulky disease, prior chemoimmunotherapy, del(11q), del(17p), TP53 without del(17p), IGHV status, region, age, prior lines of therapy and Rai stage. An efficacy analysis assessed investigator-assessed PFS (INV PFS) in randomized patients with baseline data (acala, n = 149; zanu, n = 327). Pseudo IPD for INV PFS for zanu were obtained from Kaplan-Meier curves. A safety analysis assessed odds ratios (ORs) of AEs in treated patients with baseline data (acala, n = 148; zanu, n = 324). To allow comparison of the incidence of AEs, an artificial data cut-off (Feb 21, 2020) was imposed for acala to match the zanu median treatment exposure (both 28.4 months). Results: After matching, the effective sample size of acala was 99 (66.6%; 65% male; median age 66 years). 12- and 24-month INV PFS are shown below. The MAIC hazard ratio (HR) for INV PFS is similar for acala vs zanu (HR 0.90, 95% CI 0.60–1.36). The risk of having grade ≥ 3 AE (OR 0.66, 95% CI 0.41–1.05), atrial fibrillation (AF; OR 1.32, 95% CI 0.56–3.08), grade ≥ 3 AF/atrial flutter (OR 0.60, 95% CI 0.12–2.89), grade ≥ 3 hemorrhage (OR 0.61, 95% CI 0.19–2.03) or an AE leading to discontinuation (OR 1.14, 95% CI 0.61–2.13) was similar with acala vs zanu. The risk of having a serious AE (OR 0.61, 95% CI 0.39–0.97), hypertension (any grade: OR 0.18, 95% CI 0.09–0.37; grade ≥ 3: OR 0.22, 95% CI 0.09–0.54), any grade hemorrhage (OR 0.54, 95% CI 0.34–0.87) or an AE leading to dose reduction (OR 0.30, 95% CI 0.14–0.67) was lower with acala vs zanu. Conclusions: Acala and zanu have a similar efficacy in patients with RR CLL, while acala has a lower risk of grade ≥ 3 hemorrhage, any grade and grade ≥ 3 hypertension and dose reduction due to AEs vs zanu. Limitations of MAIC analyses mean the results should be viewed as hypothesis-generating. [Table: see text]

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