New data from two different studies unveiled during the 57th ASH annual meeting highlight the efficacy and safety of Gazyvaro for the treatment of patients with previously untreated chronic lymphocytic leukaemia (CLL) who are unsuitable for fludarabine-based therapy.1

Mature analyses from the key CLL11 study demonstrate that:1

  • Gazyvaro plus chlorambucil significantly prolonged Progression Free Survival (PFS) compared to both chlorambucil monotherapy and MabThera® (rituximab) plus chlorambucil1
    • 31.1 months vs 11.1 months (p<0.0001) and 28.7 vs 15.7 months (p<0.0001) respectively1
  • Gazyvaro plus chlorambucil significantly prolonged time to next treatment (TTNT); an increase of three years compared to chlorambucil, and more than one year compared to MabThera plus chlorambucil1
    • 51.1 months vs 15.1 (p<0.0167) and 51.1 months vs 38.2 months (p<0.0001) respectively1
  • Gazyvaro plus chlorambucil significantly prolonged overall survival (OS) compared to chlorambucil (median OS not reached vs 58.5 months, p=0.0167)1
  • No new safety signals have been identified.1

In addition, results from a subgroup analysis of the Phase IIIb GREEN study, looking at the investigational combination of Gazyvaro plus bendamustine, a more potent chemotherapy, highlight that:2

  • Following treatment with Gazyvaro plus bendamustine, almost 60% and 30% of the ITT population showed no detectable sign of disease in the blood and in the bone marrow respectively, also known as minimal residual disease (MRD) negativity2
  • 78% of patients responded to treatment with Gazyvaro plus bendamustine,1 with a complete response rate of 32%1 and a further 46% of patients achieving partial response.2

"The primary aim of treatment in patients with CLL who are considered unfit for fludarabine-based therapy is to achieve durable remissions whilst maintaining quality of life. These updated CLL11 results highlight that after only 6 months of treatment with Gazyvaro plus chlorambucil, patients are treatment-free for a median of nearly four years which is an impressive outcome in this patient population" said Professor Peter Hillmen, Professor of Experimental Haematology and Honorary Consultant Haematologist at Leeds Teaching Hospitals NHS Trust. "Encouragingly, we now have emerging data that Gazyvaro can be safely combined with bendamustine and the emerging results from the GREEN study show that 28% of patients were MRD-negative in the bone marrow with this combination. We know from historical data, that patients who achieve MRD negativity have a much better outcome, with durable remissions and prolonged overall survival."

The safety profile for Gazyvaro in the GREEN subgroup population was manageable and treatment in combination with bendamustine was generally well tolerated.2 The most common grade 3-5 adverse events associated with Gazyvaro in combination with bendamustine were neutropenia (50%), infusion-related reactions (15.2%), infection (12.7%), thrombocytopenia (12.7%) and tumour lysis syndrome (10.1%).2

About the CLL11 study

CLL11 is a Phase III, multicentre, open-label, randomised three-arm study that investigated the efficacy and safety profile of Gazyvaro added to chlorambucil chemotherapy compared with MabThera added to chlorambucil or chlorambucil alone in 781 previously untreated patients with CLL and coexisting medical conditions.1, 3,4 These patients were representative of those ordinarily diagnosed and treated for CLL (the UK median age of a CLL patient is 72 years and the median age of patients in the CLL11 trial was 73 years).3,4, 5 The primary endpoint of the study was progression-free survival (PFS) with secondary endpoints including overall response rate (ORR), time to next treatment (TTNT), overall survival (OS), event free survival (EFS), minimal residual disease (MRD) and safety profile.6

About the GREEN study

The GREEN study is an ongoing, non-randomised, multi-cohort Phase IIIb study investigating the safety and efficacy of Gazyvaro alone or in combination with chemotherapy in 950 patients with previously untreated or relapsed/refractory CLL and assesses various strategies (cohorts 1-3) for reducing the rate of infusion-related reactions (IRRs) during the first infusion of Gazyvaro.2

The data presented at the ASH annual meeting reports efficacy and safety data from a subgroup of previously untreated patients (158) in cohort 1 of the GREEN study, who received at least a partial dose of both Gazyvaro and bendamustine.2 The secondary endpoints of the subgroup analysis include minimal residual disease (MRD) measured three months post-treatment and overall response rate (ORR).2 Safety endpoints included incidence, type and severity of adverse events (AEs).2