The FDA ( Food and Drug Administration ) has approved a Supplemental Biologic License Application ( sBLA ) for the use of Arzerra ( Ofatumumab ), a CD20-directed cytolytic monoclonal antibody, in combination with Chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukaemia ( CLL ) for whom Fludarabine-based therapy is considered inappropriate.
The FDA approval of the first-line indication is based on results from a Phase III study ( COMPLEMENT 1 ) which has demonstrated statistically significant improvement in median progression-free survival in patients who received the combination of Ofatumumab and Chlorambucil compared to patients who received Chlorambucil alone.
The results from COMPLEMENT 1, the randomised, open-label, parallel-arm, pivotal phase III study evaluating the combination of Ofatumumab and Chlorambucil ( n=221 ) versus Chlorambucil alone ( n=226 ) has demonstrated statistically significant improvement in median progression-free survival in patients randomised to Ofatumumab and Chlorambucil compared to patients randomised to Chlorambucil alone ( 22.4 months versus 13.1 months, respectively ) ( hazard ratio, HR=0.57 [ 95 per cent CI, 0.45, 0.72 ] p less than 0.001 ).
The primary objective efficacy measure was progression-free survival as assessed by a blinded Independent Review Committee ( IRC ) using the International Workshop for Chronic Lymphocytic Leukaemia ( IWCLL ) updated National Cancer Institute-sponsored Working Group ( NCI-WG ) guidelines ( 2008 ).
Secondary efficacy endpoints included overall response ( OR ), complete response ( CR ), and duration of response.
The majority of adverse reactions were grade 2 or lower in both treatment arms. The most common ( greater than or equal to 5% in the Ofatumumab plus Chlorambucil arm and also greater than or equal to 2% more than in the Chlorambucil monotherapy arm ) non-infusion-related adverse reactions ( all grades ) as reported by investigators within 60 days following the last treatment were neutropaenia ( 27% Ofatumumab plus Chlorambucil, 18% Chlorambucil ), asthaenia ( 8%, 5% ), headache ( 7%, 3% ), leukopaenia ( 6%, 2% ), herpes simplex ( 6%, 4% ), lower respiratory tract infection ( 5%, 3% ), arthralgia ( 5%, 3% ), and upper abdominal pain ( 5%, 3% ).
Infusion reactions were seen in 67% of patients in the Ofatumumab plus Chlorambucil arm. Ten per cent of infusion reactions were grade 3 or greater. Infusion reactions that were grade 3 or greater, serious or led to treatment interruption or discontinuation occurred most frequently with cycle 1 and decreased with subsequent infusions.
Chronic lymphocytic leukaemia, the most commonly diagnosed adult leukaemia in Western countries, accounts for approximately one-third of all cases of leukaemia. In the U.S., it is estimated that more than 105,000 people currently live with or have been previously treated for CLL, and an estimated 15,680 new cases of CLL were diagnosed in the past year.
The average age of diagnosis is 72 years old, and approximately 90% of patients with CLL are estimated to be over the age of 55. The majority of patients with CLL have at least one comorbidity such as hypertension, diabetes, cardiovascular disease, or COPD. ( Xagena )
Source: GSK, 2014