Venetoclax FDA label updated to include Minimal Residual Disease negativity data

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By: scienterrific | Last updated: 12 September 2018 | In: US FDA Onc\Haem Approvals, Haematology, Targeted Therapies

Article Keywords

Roche, CLL, rituximab, venetoclax, leukaemia, AbbVie, Venclexta, MabThera

On the 11th of September 2018, the FDA updated the label of venetoclax tablets (VENCLEXTA®, AbbVie) in combination with rituximab (MabThera®, Roche) to include information about pre-treated patients with chronic lymphocytic leukaemia (CLL) in the Phase III MURANO trial who had achieved Minimal Residual Disease (MRD)-negativity.

Clinical Data

The Phase III international, multicenter, open-label, MURANO trial (NCT02005471) randomised 389 patients with relapsed or refractory (R/R) CLL 1:1 to either receive venetoclax plus rituximab (N=194) vs bendamustine plus rituximab (N=195). All participants were pretreated with at least one line of therapy for R/R CLL before the study. The median age was 65 years (range: 22-85).

The composite primary endpoint consisted of the percentage of patients with progression disease (PD) and the progression-free survival (PFS) as assessed by an Independent Review Committee (IRC). At median follow-up of 23.4 months (range: 0.0–37.4+) the median PFS with venetoclax plus rituximab was not reached and measured 18.1 months in the bendamustine plus rituximab group (HR=0.19; 95% CI, 0.13–0.28; P<0.0001).

The secondary endpoints included the overall response rate (ORR), and included MRD evaluation by allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) in patients who achieved a partial response (PR), a complete response (CR), or a CR with incomplete marrow recovery (CRi). The trial defined MRD negative status as less than one CLL cell per 10,000 lymphocytes.

The MRD-negativity rate in the peripheral blood at nine months was 53% (103/194) in the venetoclax plus rituximab group vs 12% (23/195) in the bendamustine plus rituximab group. At the same time point, the MRD-negativity rate in patients with a CR or CRi was 3% (6/194) for venetoclax plus rituximab and 2% (3/195) for bendamustine plus rituximab.

Safety

The most common (in ≥20% of patients) any-grade adverse reactions (AR) for venetoclax plus rituximab were neutropenia (65%), diarrhoea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%) and nausea (21%). Sixteen per cent of patients discontinued the combination venetoclax plus rituximab for ARs. Dose reduction and dose interruptions were reported in 15% and 71% of patients, respectively. Neutropenia was a major cause (46% of patients) for dose interruptions in the venetoclax plus rituximab arm; neutropenia and thrombocytopenia both led to discontinuation of 3% of patients.

Serious ARs in ≥5% of patients with the combination venetoclax plus rituximab were reported in 46% of patients, the most frequent being pneumonia (9%). Grade 5 ARs occurring in the absence of PD and within 30 days of the last venetoclax dosing and/or 90 days of the last rituximab dosing were reported in 2% (4/194) of patients.

In the bendamustine plus rituximab group, 10% of patients discontinued for ARs. Dose reduction and dose interruptions were reported in 15% and 40% of patients, respectively.

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Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).

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