The E1912 trial was designed to compare standard fludarabine cyclophosphamide and rituximab, or FCR, chemoimmunotherapy, our current gold standard treatment for younger CLL patients, to a novel combination of ibrutinib and rituximab in previously untreated CLL patients aged 70 and younger. What the trial result has found is an improvement in both the progression free survival and overall survival for the novel therapy arm. Notably, the novel combination also was less likely to have serious side effects than the standard arm so one of those rare circumstances that we hope for where the newer treatment is both more effective and less toxic. In combination with the Alliance trial for elderly patients presented in the plenary session, these two studies really move CLL therapy fully into the novel therapy or targeted therapy era as of ASH 2018 and establish ibrutinib-based therapy as a preferred initial treatment for CLL patients, largely independent of age.
There were 529 patients enrolled in the ECOG trial. They were randomised in a two to one manner, so two out of every three patients enrolled were randomised to the experimental arm, one to the standard therapy arm.
The adverse effects: overall grade 3 and higher adverse events were more common in the FCR arm, a little over 70% had at least one grade 3 or higher adverse event as opposed to more in the 58% range in the ibrutinib arm. Worth noting that different drugs obviously have some different side effects and in that regard the standard chemotherapy-based arm had more myelosuppression and increased risk of infection. On the ibrutinib arm atrial fibrillation events which occurred at grade 3 or higher in 3% of patients and grade 3 or higher hypertension which occurred in 7% of patients were more common in the experimental arm. But overall fewer grade 3 and higher adverse events for the novel therapy arm.
The take-home message is that ibrutinib-based therapy is now the single most effective therapy in first line CLL, beating our previous gold standard of FCR. Also better tolerated than FCR-based therapy and is a treatment option that should be preferred or at minimum discussed with all CLL patients initiating first line treatment.