Nitin Jain, MD, discusses the preliminary results of a study investigating allogeneic chimeric antigen receptor T-cell therapy with lymphodepletion in patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
Nitin Jain, MD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, discusses the preliminary results of a study investigating allogeneic chimeric antigen receptor (CAR) T-cell therapy with lymphodepletion (LD) in patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
The phase 1, open-label, dose-escalation BALLI-01 study (NCT04150497) was designed to determine the safety, tolerability, and maximum tolerated dose of UCART22, an off-the-shelf allogeneic CAR T-cell product. Previous trial cohorts used an LD regimen of fludarabine and cyclophosphamide. In the cohort discussed by Jain, patients received reduced levels of chemotherapy and a modified LD regimen that also included alemtuzumab (Lemtrada) to more effectively deplete T-cells and ensure CAR T-cells can expand and persist in the body longer.
The primary end points were adverse events [AEs], serious AEs, and dose-limiting toxicity. According to Jain, 12 patients were treated, but 1 could not receive the CAR T-cell infusion. Two out of 6 who received the modified LD were evaluated had a bone marrow blast reduction to below 5%, demonstrating early clinical activity of CAR T-cell therapy. Mild to moderate cytokine release syndrome (CRS) was observed in 3 patients, while 1 patient had skin graft-vs-host disease (GVHD) that required hospitalization and none experienced immune effector cell-associated neurotoxicity syndrome (ICANS) or UCART22-related grade 3 or higher AEs.
The early results showed promising tolerability and efficacy for the modified LD regimen. Jain says that the next dose level will give patients a higher dose of CAR T cells with the same LD regimen.
0:08 | Overall, we have treated 12 patients on the study, and 11 patients got the drug. One patient could not get the CAR T [-cell] infusion. So, [an] important point is that when we have intensified the LD by adding alemtuzumab, but by cutting down on the chemotherapy dose, we added alemtuzumab. But with this modified LD, we are seeing the activity of the CAR [T-cells] in terms of more CAR T persistence, or at least we are seeing CAR T expansion. And then some of these patients are having clinical responses. As I said, 2 out of 6 patients had a bone marrow blast reduction in less than 5% range after getting the UCART22.
So in terms of the CRS and ICANS, which are the important aspects of CAR T, 3 patients had [AEs]:  of the 6 patients had CRS, grade 1 or 2 CRS…no patient had ICANS, and there's 1 patient who had skin GVHD, which can also occur with this allogeneic product, but this was easily manageable. So overall, I think the data points to that with this modified LD, we are achieving what we wanted to achieve. We're seeing more CAR T expansion; we are seeing some early results of clinical activity. And now what we have done is that the trial is ongoing, and the next dose level, which is dose level 3, is currently accruing patients at a higher CAR T dose level with the same LD, and we'll have to see how that pans out.