Overview of Allogeneic CAR T-Cell Therapy Trials for ALL, AML, and NHL

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

As opposed to autologous CAR T-cell therapies, allogeneic CAR T cells do not need to be derived from leukapheresis of the patient and can be made available more quickly. Jain highlights the CALM trial (NCT02746952) of UCART19, an anti-CD19 allogeneic CAR T-cell therapy, in which there was a 67% complete response rate among 21 patients with B-ALL. In this trial, the treatment served as a bridging therapy to hematopoietic cell transplant since the cells did not persist long term.

Another allogeneic CAR T product, PBCAR0191, was investigated in a trial (NCT03666000) of patients with ALL and non-Hodgkin lymphoma. Its results were presented at the 2021 American Society of Hematology (ASH) annual meeting and showed clinical activity in patients including some who had received prior autologous CAR T-cell therapy.

Other ongoing clinical trials noted by Jain include the phase 1/2 BALLI-01 (NCT04150497) trial of UCART22 for B-ALL, the phase 1 trial (NCT03190278) of UCART123 for acute myeloid leukemia, and a phase 1 trial (NCT04629729) of FT819 for B-cell malignancies. He says more data may be presented in the next year from various trials.

TRANSCRIPTION:

0:08 | One of the trials is [for] a product called UCART19, which I believe was the first trial in the United States with allogeneic CAR T cells for B-ALL. That was published last year in the journal Lancet, where 21 patients were treated with B-ALL. We saw that there were relatively high rates of responses in about 60% to 70% of the patients. And more so, I would say, it was a bridge to transplant because these CAR T cells do not last forever. Therefore, most of these patients then consulted with a transplant.

Another trial is by a company called Precision Biosciences. We had an oral presentation at ASH last year, where again these allogeneic CAR [T cells] derived from healthy human donors were able to show clinical activity, both for ALL as well as for non-Hodgkin lymphoma. I should say there are several other clinical trials in development, including for UCART22, UCART123 for AML, Fate Therapeutics [FT819]. There are many other companies which are developing off-the-shelf allogeneic CARs, and hopefully we'll see some data maybe at this upcoming ASH or in next year’s meetings as well.