Use of GA101 and Clb preferable to rituximab in elderly or unfit chronic lymphocytic leukaemia patients
Dr Valentin Goede - University of Cologne, Cologne, Germany
This is a three-armed trial run in older and less fit CLL patients comparing a chlorambucil mono-chemotherapy with chemo-immunotherapy where chlorambucil is combined with either the CD20 antibody rituximab or a new CD20 antibody called obinutuzumab or GA101. What we are presenting here is the head to head comparison of the two antibody arms actually, so the GA101 arm compared with the rituximab arm. The basic trial results are that GA101 combined with chlorambucil is more efficacious than rituximab combined with chlorambucil in this particular patient population with regard to treatment response rates, also to molecular responses and finally the primary endpoint of the trial, progression free survival. So patients receiving that new antibody, GA101, in combination with chlorambucil have a better outcome than patients receiving rituximab in combination with chlorambucil.
Which patients do you look at?
This is a trial in older and less fit CLL patients though we examined 781 patients it’s a large trial. The median age in that trial was 73, 74 years, almost half of the patients were older than 75 years. Importantly, these older patients also had a significant comorbidity burden, so typically these patients may have, in that age group, cardiovascular diseases, respiratory diseases, also diabetes, musculoskeletal problems, renal impairment. All of these diseases make these patients less suitable for standard CLL treatment, so aggressive treatment approaches. So this was a patient population that is not well eligible for standard treatment due to age and comorbidity.
What could be the impact of this data?
In many countries chlorambucil monotherapy has been a standard treatment of this particular patient population for a long time. I think this trial now shows that adding a CD20 antibody is beneficial in these patients and significantly improves patient outcome, including overall survival which has been shown for the combination of GA101 plus chlorambucil in our trial compared to chlorambucil alone. One important outcome of the trial is that the reference treatment for these patients has changed and that chemo-immunotherapy is now established not only in younger patients with CLL, as it was before, but also in these elderly patients.
A second important outcome of the trial is related to the comparison of the two antibody uses in this trial. Because the trial shows that combining GA101 with chlorambucil is better than using rituximab for that combination treatment. This is important because GA101 is a so-called engineered antibody with features of a so-called type 2 antibody whereas rituximab is a type 1 antibody. This trial shows that at least in this setting examined in our trial the antibody engineering leads to better anti-CD20 treatment in CLL. This is an important step in the improvement of anti-CD20 treatment of CLL in general. We know that anti-CD20 targeting in CLL is very important because it has been shown now several times that it can improve overall survival of the patient and can indeed change the course of the disease of the patients.