In patients who receive CAR T-cell therapy for ALL we see a very high response rate and the possibility of durable remissions in the majority of patients. But there are some patients who lose their CAR T-cells early on and we have observed a higher risk of relapse in those patients. So we wanted to identify ways that we could potentially improve upon their durable responses and hope to, in doing that, to have their CAR T-cells last longer to try to surveil for leukaemia and decrease the risk of relapse. So we hypothesised in those patients who lose their CAR T-cells early that immune checkpoint pathways may play a role in that loss of T-cell persistence and that blocking an immune checkpoint pathway may lead to improved function and persistence of CAR T-cells. So in a group of patients who had had short persistence of their CAR T-cells or who had had a partial or no response to CAR T-cell therapies we asked whether the addition of PD-1 blockade may improve their outcomes.
What did you find?
We tested this in three groups of patients. In patients who had had no response to CAR T-cell therapies we saw the potential for some transient effects but ultimately four out of the four patients treated progressed and so did not have a complete response to CAR T-cells in this combination. But in two other groups we did see a benefit. One group was the group of patients who lost their CAR T-cells very early on and we found that the combination of reinfusion of CAR T-cells with PD-1 blockade extended the persistence of their CAR T-cells in half of the patients that we treated. In the third group of patients who had bulky extramedullary disease, which in many ways acts more like lymphoma, we saw that two of the four patients treated had a partial response and two of the four patients had a complete response.
What implications can be taken from this?
What this shows us is that if we are to investigate the mechanism behind why some patients do not have a response to CAR T-cell therapy or do not have a durable response, that we may be able to identify patients who may benefit from this and we may be able to maximise the outcomes with CAR T-cell therapy.