The pharmacokinetics (PK) of venetoclax in the CAVALLI study were adequately described using a previously developed legacy population pharmacokinetics (PopPK) model, with study-specific (CAVALLI) effects on apparent clearance (CL/F) and apparent central volume of distribution (V2/F) added to the PopPK model to account for the possible differences between the population of CAVALLI study patients relative to the population of patients from the prior analysis.

Encouraging outcomes for efficacy were achieved without compromising delivery of rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy; increased venetoclax exposures did not translate into improved efficacy for investigator-assessed progression free survival (INV-PFS) and positron emission tomography-computed tomography assessed complete response (PET-CR) rates in all-comers or BCL-2-IHC-positive subpopulations.

Venetoclax plus R-CHOP demonstrated increased but manageable toxicity versus R-CHOP alone, with adverse events expected on the basis of the mechanism of action of venetoclax and consistent with the toxicity profile of R-CHOP. Data did not suggest that higher doses of venetoclax would cause additional toxicity compared with lower doses of venetoclax within the CAVALLI study.