EHA 2016

Blinatumomab improves survival in ALL patients

Prof Max Topp - University of Würzburg, Würzburg, Germany

Good morning everyone and thank you for giving us the opportunity to brief you about which I believe is exciting results. I will report on blinatumomab that can improve overall survival in patients with relapsed and refractory Philadelphia negative B precursor ALL. This is an open label phase III randomised trial.

Blinatumomab in ALL is a success story that has been going on for a couple of years and blinatumomab is an immunotherapy agent that combines two antibody constructs fused together creating an artificial chimeric protein which will enable T-cells to recognise every single B-cell and malignant B-cell in humans. The fate of the leukemic cells is once they are engaged with T-cells that the T-cells are able to punch in holes into these target cells and leading into apoptosis the T-cells start to proliferate and are capable of becoming serial killers.

So what is the data currently with blinatumomab? Blinatumomab has been shown in a phase II trial to be highly efficacious in patients with relapsed refractory ALL. Blinatumomab is now licensed to be given in patients with relapsed refractory ALL.

The purpose of this study was to compare if blinatumomab versus standard chemotherapy can outpace patients in this situation in terms of overall survival which was the primary endpoint of this trial. Secondary endpoints were complete remission during induction and also event free survival as well as other secondary endpoints, the molecular remission rate, the realisation of allo-transplantation in these patients and of course the incidence of adverse effects.

In the intent to treat analysis blinatumomab was able to double the overall survival of this dismal patient population from 4.0 months to 7.7 months. It appears, this graph, that those patients potentially even cured with blinatumomab even not doing a transplantation in this situation. Considering the adverse events, blinatumomab versus standard chemotherapy on the left. Here we have a very well-balanced situation, we have grade 3 adverse events being evenly distributed between the SOC treated arm and the blinatumomab treated arm, also grade 4 and the fatal AEs. Fatal AEs are all related to chemotherapy or leukaemia death in this context of bleeding and infection. Considerably of interest is the rate of neutropenia in these patients and infection, neurological events and cytokine release syndrome. Both neutropenia infection seem to be less common in patients treated with blinatumomab and of course what was very important for us to demonstrate that neurological events are similarly distributed between the SOC treated arm and the blinatumomab treated arm. Cytokine release syndrome which is the hallmark of T-cell therapy and has been shown to be in CARTs is detrimental to patients, leading to ICU, was also seen in 5% of the patients and all the patients died due to cytokine release syndrome.

So, in summary, blinatumomab is the first immunotherapy agent to demonstrate overall survival benefit when compared to chemotherapy in patients relapsing with adult lymphoblastic leukaemia. It increases almost twofold the overall survival when compared to standard of care. This was also consistent in all subgroups that we were looking at, regardless of age, prior salvage therapy or patients relapsing after allo-transplantation. It also looks at the adverse events that were observed here were consistent with previously known blinatumomab adverse events and, of note, neutropenia infection and neurological events seem to be not increased with the use of blinatumomab in this patient cohort.