We do have now antibody-drug conjugate inotuzumab, the BiTE blinatumomab and the CAR T-cells. The main question is how to use these three new approaches, what should be the first to be used in a clinical setting? Can we use one and then after the other? Because they are targeting sometimes the same antigen so it’s difficult to come with another drug targeting the same antigen after failure of a drug like that.
At the present time we do not have the answer and I guess the speaker who is focussed on CAR T-cells the question is in the relapsed refractory setting how CAR T-cells can be used to induce a new remission and even to prolong the second remission or further remission and allow us to not transplant the patient. So the balance between CAR T-cell and transplantation is important in that setting, especially after relapse of the disease.
For the bispecific the main issue is how to introduce bispecific into frontline treatment in order to reduce the relapse incidence. At the present time it’s done mostly in patients with higher risk of relapse which were these patients who were these patients eligible for stem cell transplantation. So the bispecific is used at the present time mostly to bridge high risk patients to transplantation in a better condition without using intensive chemotherapy and with a better effect on the disease, allowing us to transplant a patient with a lower minimal residual disease level. So blinatumomab is most used as that – to bridge a patient to transplantation. The next issue will be should we continue to transplant the patients after blinatumomab. So that’s another important question for the next future.
Do you think we could see studies looking at a possible combination of blinatumomab and CAR T-cell therapy?
There are still some studies running with a combination of… I mentioned blinatumomab plus tyrosine kinase inhibitors, so two new drugs. There are some studies combining blinatumomab and inotuzumab sequentially which is also very interesting. Blinatumomab and CAR T-cells the main issue is if we use blinatumomab which is directed against the CD19 antigen some relapses after blinatumomab are associated with a loss of the target so there is no more CD19 expression on the cell surface of the blast. So this is an issue when you want to continue a treatment targeted to the same antigen. So the sequential administration of blinatumomab plus CAR T-cells is questionable. It could be efficient in some patients but it could not be efficient in some others. Actually in the first CAR T-cell trial with Kymriah blinatumomab exposure prior to CAR T-cell was an exclusion criteria.