Venetoclax approved by FDA for untreated CLL and SLL

The U.S. Food and Drug Administration has approved venetoclax for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). Approval was granted on 15 May 2019, based on the CLL14 trial (NCT 02242942).

This randomized, multicenter, open label, actively controlled trial investigated venetoclax in combination with obinutuzumab (VEN+G) versus obinutuzumab in combination with chlorambucil (GClb). A total of 432 patients with previously untreated CLL and coexisting medical conditions, were enrolled on the study.

An independent review committee assessed progression-free survival (PFS) – the major efficacy outcome. The results of the trial showed a statistically significant improvement in PFS for patients who received VEN+G, in comparison to those who received GClb (HR 0.33; 95% CI, 0.22—0.51; P < 0.0001).

This approval follows a breakthrough therapy designation in March 2019, and is based on results that showed the combination, VEN+G, was able to achieve a durable and significant reduction in disease worsening or death in comparison to the standard first-line therapy GClb.

Venetoclax has already been approved for use in previously-treated adults with CLL or SLL, and in combination with azacytidine, decitabine or low-dose cytarabine for certain adults with newly-diagnosed acute myeloid leukemia (AML).

In the CLL14 study, median PFS was not reached in either arm after a median follow-up of 28 months. The overall response rate in the VEN+G arm was 85%, compared with 71% in the GClb arm, P = 0.0007. Statistically significant improvements in the rates of minimal residual disease negativity in bone marrow and peripheral blood was demonstrated through the trial.

Common adverse reactions of venetoclax in patients with CLL or SLL affecting more than 20% of participants, when given in combination with obinutuzumab, rituximab or as monotherapy, were neutropenia, thrombocytopenia, anemia, diarrhea, nausea, cough, upper respiratory tract infection, musckoskeletal pain, fatigue and edema.

The full prescribing information can be found here.