Venclyxto in combination with Gazyvaro for patients with previously-untreated chronic lymphocytic leukemia, approved in European Union
The European Commission ( EC ) has approved Venclyxto ( Venetoclax ) in combination with Gazyvaro ( Obinutuzumab ) for the treatment of adult patients with chronic lymphocytic leukemia ( CLL ) who were previously untreated.
The approval is based on results from the phase 3 CLL14 clinical trial primary analysis ( median follow up of 28 months ), which has demonstrated superior progression-free survival ( PFS ) as assessed by investigators in patients treated with Venetoclax plus Obinutuzumab compared to patients who received a standard of care chemotherapy regimen of Chlorambucil plus Obinutuzumab ( hazard ratio, HR=0.35; 95% CI ( 0.23 - 0.53 ), p less than 0.0001, medians not yet reached ).
At an updated CLL14 efficacy analysis ( median follow-up of 40 months ), the median PFS had not been reached in the Venetoclax + Obinutuzumab arm and was 35.6 months [ 95% CI: 33.7 - 40.7 ] in the Obinutuzumab + Chlorambucil arm ( HR=0.31; 95% CI: 0.22 - 0.44 ).
The 36-month PFS estimate in the Venetoclax plus Obinutuzumab arm was 81.9% [ 95% CI: 76.5, 87.3 ] and in the Obinutuzumab plus Chlorambucil arm was 49.5% [ 95% CI: 42.4, 56.6 ].
Additionally, after completing one year of treatment, patients treated with Venetoclax plus Obinutuzumab experienced deep response as measured by higher rates of undetectable minimal residual disease ( MRD ) or complete response ( CR ) as compared to patients receiving a standard of care regimen.
In the trial, adverse events were consistent with the known safety profiles of Venetoclax and Obinutuzumab alone.
At least one adverse event of any grade occurred in 94.3% of patients in Venetoclax plus Obinutuzumab arm.
The most common grade 3-4 adverse events were neutropenia and infections.
Tumor lysis syndrome was reported in three patients in the Venetoclax plus Obinutuzumab group ( all during treatment with Obinutuzumab and before Venetoclax ).
The randomized, multicenter, open-label, actively controlled CLL14 trial, which was conducted in close collaboration with the German CLL Study Group ( DCLLSG ), has evaluated the efficacy and safety of a combined regimen of Venetoclax and Obinutuzumab ( n=216 ) versus Obinutuzumab and Chlorambucil ( n=216 ) in patients with previously-untreated CLL and coexisting medical conditions ( total Cumulative Illness Rating Scale [ CIRS ] score more than 6 or creatinine clearance less than 70 mL/min ).
The therapies were administered for a fixed duration of 12 cycles for Venetoclax in combination with six cycles of Obinutuzumab. Cycles were comprised of 28 days.
The trial enrolled 432 patients, all of whom were diagnosed according to the International Workshop on Chronic Lymphocytic Leukemia ( iwCLL ) criteria and were previously untreated.
The primary efficacy outcome was PFS as assessed by the investigator. Key secondary endpoints were MRD-negativity in peripheral blood and bone marrow, and overall and complete response rates.
Chronic lymphocytic leukemia is a slow-growing form of leukemia in which too many immature lymphocytes are found predominantly in the blood and bone marrow.
In 2018, approximately 95,000 new cases of leukemia were diagnosed in Europe.
CLL is the most common form of leukemia in the Western Hemisphere, accounting for approximately one third of new leukemia diagnoses. ( Xagena )
Source: Abbvie, 2020