Nitin Jain, MD

Nitin Jain, MD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, discusses the significance of a study of UCART22, an allogeneic chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

CAR T-cell therapies are now approved by the FDA for lymphomas, multiple myeloma, and leukemia. UCART22 differs from currently approved therapies in 2 key ways, according to Jain. First, it targets the CD22 antigen, while existing therapies commonly target CD19 as a biomarker. CD22-targeted CAR T-cell therapies are not yet approved and there is limited clinical data on their efficacy so far.

Second, UCART22 is an off-the-shelf CAR T-cell product, making it more easily available. Patients do not need to undergo leukapheresis and wait for the CAR T cells to be manufactured before infusion.

The phase 1, open-label, dose-escalation BALLI-01 study (NCT04150497) is investigating the safety, tolerability, and maximum tolerated dose of UCART22 with lymphodepletion to improve efficacy. After reporting results from the first cohort who are receiving UCART22 and lymphodepletion, Jain says the next step is to observe CAR T-cell persistence and clinical activity at a higher dose level.

 Overall, I think the field of CAR T has continued to expand tremendously. You know, we already have approved products for both lymphomas, myeloma, and leukemias now, and including ALL. So I think this UCART22 represents another aspect of treating patients with a different target than CD19. Right now, none of the CD22-targeting [CAR T cells] are FDA approved. And the clinical data with CD22 targeting is actually quite limited. So the advantage, also, of UCAR products is that this is an off-the-shelf product so it's readily available to the patients. You don't have to wait for leukapheresis; you can give it to patients right away. So we hope and we'll have to see how this next year pans out, where we have to enroll patients at the next dose level, look for the safety [and] efficacy, and hopefully we'll see more CAR T persistence and clinical activity at the next dose level.

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Nitin Jain, MD, discusses the significance of a study of UCART22, an allogeneic chimeric antigen receptor T-cell therapy for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. 

Off-The-Shelf CAR T-Cell Therapy Targets CD22 in B-ALL

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.

 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]: [3] 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.

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. 

Lymphodepletion Improves Results for Allogenic CAR T-Cell Therapy in ALL

Nitin Jain, MD, assistant professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses a phase II trial combining nivolumab (Opdivo) with ibrutinib (Imbruvica) for chronic lymphocytic leukemia (CLL) and richter transformation (RT) during the American Society of Hematology (ASH) Annual Meeting.

Nitin Jain, MD, assistant professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses a phase II trial combining nivolumab (Opdivo) with ibrutinib (Imbruvica) for chronic lymphocytic leukemia (CLL) and richter transformation (RT) during the American Society of Hematology (ASH) Annual Meeting.<br />
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An Overview of a Study Combining Nivolumab With Ibrutinib in CLL and Richter Transformation

Nitin Jain, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, discusses the checkpoint inhibitors under investigation in chronic lymphocytic leukemia (CLL).

Nitin Jain, MD | Authors

Articles

Off-The-Shelf CAR T-Cell Therapy Targets CD22 in B-ALL

Lymphodepletion Improves Results for Allogenic CAR T-Cell Therapy in ALL

An Overview of a Study Combining Nivolumab With Ibrutinib in CLL and Richter Transformation

New Checkpoint Inhibitors Under Investigation in CLL