On 15 May 2019, the FDA approved venetoclax (Venclexta®, AbbVie/Genentech) for the treatment of adult chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) patients.

CLL14

The FDA approval was based on the multicentre, open-label, actively controlled CLL14 trial (NCT02242942) which randomised 432 previously untreated CLL patients with coexisting medical conditions 1:1 to receive venetoclax plus obinutuzumab vs obinutuzumab plus chlorambucil. The primary efficacy endpoint was the progression-free survival (PFS) as assessed by an independent review committee.

The CLL14 study showed a significant PFS improvement for patients treated with venetoclax plus obinutuzumab vs obinutuzumab plus chlorambucil (HR=0.33; 95% CI, 0.22-0.51; P<0.0001). After a median 28 months follow-up, the overall response rate measured 85% in the venetoclax plus obinutuzumab arm compared to 71% in the obinutuzumab plus chlorambucil arm (P=0.0007). Moreover, the study demonstrated a statistically significant improvement in the rate of minimal residual disease negativity (<1 CLL cell per 104 leukocytes) for bone marrow and peripheral blood. The median PFS and overall survival data were not yet mature.

Safety

Common adverse reactions in ≥20% of CLL/SLL patients treated with venetoclax plus obinutuzumab, rituximab, or as monotherapy included neutropenia, thrombocytopenia, anaemia, diarrhoea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and oedema.

Full prescribing information Venclexta®.