The Future of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia

Nitin Jain, MD, associate professor in the department of leukemia, division of cancer medicine, at The University of Texas MD Anderson Cancer Center, discusses future improvements he anticipates for autologous and allogeneic chimeric antigen receptor (CAR) T-cell therapies for B-cell acute lymphoblastic leukemia (B-ALL) and other hematologic malignancies.

Jain discussed research into ‘off-the-shelf’ allogeneic CAR T-cell therapies that avoid the need for leukapheresis which delays the treatment of patients. Although they have shown efficacy, their overall response rates are not equal to that of autologous CAR T cells, to which the vast majority of patients have a response. Jain says that more research is needed to improve response rates so that allogeneic therapies can be a viable alternative, used more rapidly, and made more widely available.

Additionally, he says CAR T-cell therapies need more data supporting their use in earlier lines of therapy. Patients are likely to have better outcomes if they receive CAR T-cell therapy before multiple lines of chemotherapy, like those in the clinical trials that led to FDA approval. Some trials are being designed to establish the efficacy and safety of earlier CAR T-cell therapy, but Jain says he sees it as valuable in early lines, particularly in patients with lower tumor burden who have detectable minimal residual disease.

TRANSCRIPTION

0:08 | In terms of next steps, I think we have to figure out more for the allogeneic CAR T-cell space. We must figure out the clinical activity of these CAR [T-cell therapies] to make sure that they are on par with what we are seeing with our autologous CAR [T-cell therapies]. That's the first step because so far, we are not seeing as high response rates as we have seen with the autologous CAR T-cell setting.

The second step for ALL as a field is to introduce these CAR [T-cell therapies] in the early months of therapy. We don't want patients to have 4 to 5 chemotherapy regimens before they're coming to CAR T cells. We probably should be doing CAR T cells in earlier lines of therapy. Some trials are being designed right now, but the approval is for relapsed/refractory ALL, so we should not wait. I think for multiple lines of therapy, earlier lines of therapy, and in lower tumor burden minimal residual disease–positive patients, that is where the field of CAR T-cell therapy is moving.