Fixed-duration acalabrutinib-venetoclax with or without obinutuzumab in CLL: Interim analysis of the AMPLIFY trial

Acalabrutinib is a highly selective BTKi with improved safety and tolerability vs ibrutinib.1 During the 66th ASH Annual Meeting and Exposition, Jennifer Brown presented the interim analysis of the phase III AMPLIFY trial (NCT03836261) evaluating the efficacy and safety of fixed duration acalabrutinib-venetoclax with/without obinutuzumab vs chemotherapy in treatment-naïve patients with CLL.2

Key learnings

At a median follow-up of 40.8 months, IRC-assessed PFS was longer in both the AV vs FCR/BR (HR, 0.65; 95% CI, 0.49–0.87; p = 0.0038) and AVO vs FCR/BR arms (HR, 0.42; 95% CI, 0.30–0.59; p < 0.0001).

PFS was prolonged in the uIgHV subgroup in AV vs FCR/BR (HR, 0.69; 95% CI, 0.48–0.97) and AVO vs FCR/BR arms (HR, 0.35; 95% CI, 0.23–0.53).

OS was prolonged in the AV vs FCR/BR arm (HR, 0.33; p < 0.0001), and was prolonged with both AV and AVO vs FCR/BR when censoring for COVID-19 deaths.

The EOT uMRD (10−4) rates were higher in the AVO vs AV and FCR/BR arms (67.1% vs 34.4% vs 45.5%) in the ITT population. The incidence of cardiac toxicity remained low in both the AV and AVO arms.

Results from the AMPLIFY trial show that a fixed-duration AV and AVO regimen vs chemotherapy resulted in improved PFS in treatment-naïve patients with CLL.

Abbreviations: AV, acalabrutinib-venetoclax; AVO, acalabrutinib-venetoclax-obinutuzumab; BTKi, Bruton’s tyrosine kinase inhibitor; CI, confidence interval; CLL, chronic lymphocytic leukemia; EOT, end of treatment; FCR/BR, fludarabine, cyclophosphamide, rituximab/bendamustine, rituximab; HR, hazard ratio; IRC, independent review committee; ITT, intention-to-treat; OS, overall survival; PFS, progression-free survival; uIgHV, unmutated immunoglobulin heavy-chain variable region; uMRD, undetectable measurable disease.