Blinatumomab vs chemotherapy as post-reinduction therapy in HR/IR first relapse of B-ALL in children and adolescents
Dr Patrick Brown - Johns Hopkins University, Baltimore, USA
This was a trial that was done by the Children’s Oncology Group which is a group of a little over 200 centres that treat children and young adults with cancer. The trial was in relapsed ALL, acute lymphoblastic leukaemia, and specifically B lineage ALL. The trial was designed to try to improve on the cure rates of standard of care for this situation and the standard of care would be a month of chemotherapy, followed by two additional blocks of chemotherapy, followed by bone marrow transplant when patients achieve a second remission. The question we asked on the trial is whether one of the new immunotherapy drugs called blinatumomab could improve on chemotherapy as consolidation therapy prior to bone marrow transplant.
Patients between the ages of 1 and 30 were enrolled on the trial and after the first month of chemotherapy were randomised to either receive more chemotherapy, that was the control arm, versus the blinatumomab which was the experimental arm. Then they all went to transplant after receiving the randomised therapy. We are very excited to share at this meeting that the results show that the experimental arm, the blinatumomab arm, showed about a 20% improvement in cure rates compared to the control arm. So this really has established a new standard of care for these patients that traditionally have had a very low cure rate.
The main conclusions were that the experimental arm, the blinatumomab, resulted in lower rates of toxicity and higher rates of conversion of patients from a state of having residual disease in their bone marrow, so-called MRD positive, to MRD negative and then also a higher proportion of patients successfully reaching bone marrow transplant. Ultimately those three factors translated into a better overall survival and that was the primary endpoint of the study was could we at the end of the day cure more patients with the immunotherapy than with standard chemotherapy. In fact we were able to do that.
These results really are going to apply to patients up to the age of 30 because those are the patients that were eligible for the trial. In fact, in older adults the imperative to use immunotherapy instead of chemotherapy is even stronger because older adults don’t tolerate standard chemotherapy nearly as well as younger patients do. So in the older adults actually the immunotherapy is being used even earlier in the disease process than it is in children and young adults. So while the cure rates have not quite gotten there for the older adults, that’s mostly because the older adults also have a harder time with bone marrow transplant. So the hope is that the immunotherapies can be optimised such that the older adults can have better survival but without requiring a bone marrow transplant.
Blinatumomab is already FDA approved but in the multiply relapsed and refractory setting and also for the setting of patients with residual disease positivity after receiving chemotherapy. So what this will do is it will extend the indication and will provide confirmatory evidence for the FDA indication that already exists. The FDA had granted conditional accelerated approval to blinatumomab for the MRD positive setting and this study was one of the confirmatory studies that was required to be positive if the drug was going to keep that indication. And it has in fact been positive and so we suspect that the drug will be able to remain available for patients through the FDA approval process for the future as well.