Allogeneic CAR T-Cell Therapy May Provide Alternate Options in ALL

Nitin Jain, MD

With an influx of clinical trials evaluating novel agents, the use of chimeric antigen receptor (CAR) T-cell therapy for the treatment of patients with acute lymphoblastic leukemia (ALL) is growing.

Investigators find CAR T cells so useful for patients with ALL due to their easy availability. Not only can patients receive immediate treatment, but they can get access to off-the-shelf CAR T-cell agents.

As of now, most of the approved CAR T-cell products are autologous CAR T cells. However, allogeneic CAR T cells are being further investigated to see if they show equal efficacy.

During a session at the 10th Annual Meeting of the Society of Hematologic Oncology (SOHO), Nitin Jain, MD, gave a presentation on the ongoing research and use of allogeneic CAR T cells within the ALL space.

“I think it's a space which is evolving, and we have to see how things pan out in the next 1-2 years. If allogeneic CARs were to show equal efficacy to autologous CARs, that will be the game changer in terms of how we are approaching CAR T-cell therapy for these patients,” stated Jain, associate professor in the department of leukemia, division of cancer medicine, at the University of Texas MD Anderson Cancer Center, in an interview with Targeted Oncology^TM.

In the interview, Jain further discussed the ongoing research of allogeneic CAR T cells as treatment for patients with ALL. He also notes what future research must examine to further the field.

Targeted Oncology: Can you explain the session you were a part of at SOHO this year?

Jain: We had 3 fantastic talks. One talked about the pediatric data and the younger data in ALL. Another talk was on minimal residual disease [MRD] in ALL, and the third talk, which I gave, was in the allogeneic CAR T cells. Overall, I think it was good to see that there are different aspects of things which are being developed. We learned what continues to be important for children and young adults, and we also learned that MRD techniques are being refined. There are next generation sequencing technologies which are coming along more in the context of ALL.

In the talk I gave on allogeneic CAR T cells, I think it's a space which is evolving, and we have to see how things pan out in the next 1-2 years. I think if allogeneic CARs were to show equal efficacy to autologous CARs, that will be the game changer in terms of how we are approaching CAR T-cell therapy for these patients.

What are some of the most recent advances seen with CAR T cells for patients with ALL?

The field of CAR T cells have moved rapidly in the last few years. Most of the approved CAR T products right now are autologous CAR T cells, which are T cells derived from the patients after leukapheresis which drive these T cells and make them into CARs. The field of allergenic CAR T cells is evolving, where you derive the T cells not from the patient, but from either a healthy donor, or for umbilical cord blood, or for some kind of a cell line. These are a new wave of CAR T cells which are in clinical trials right now.

The advantages are these CAR T cells are available right away. You don't have to wait for leukapheresis, you don't have to wait for bridging chemotherapy, and they're available off the shelf. These can be given to patients almost right away, which is the biggest advantage of these CAR T cells. Obviously, there is limited data available at this time in terms of clinical data to these CAR T cells compared with what we know about autologous CAR T cells.

What CAR T products are approved for ALL?

For acute lymphoblastic leukemia in the United States, there are 2 CAR T cells which are approved. One is in the pediatric patient population up until the age of 25 years, and the other is for those 18 years and older. The pediatric 1 is made by Novartis and is called tisagenlecleucel [Kymriah]. For adults, the approved CAR T is brexucabtagene autoleucel [Tecartus], which is made by Kite pharmaceutical company. These are 2 CD19 autologous CARs, which are approved in the United States and eligible for any relapsed/refractory ALL patients.

The allogeneic CARs are a new field of CAR T cells which are being developed and several companies are doing trials in this space. Some of this data has been published, either in full manuscript form or abstract form, and some other trials are just starting off.

Can you discuss some of the ongoing trials examining CAR T cells in ALL?

There are a couple of trials, including UCART19 which was a trial [NCT02746952] in the United States with allogeneic CAR T cells for B-cell ALL. [Those results were] published last year where 21 patients were treated with B-cell ALL. We saw that there were high rates of responses in about 60%-70% of the patients, and more. 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.

We had an oral presentation at the American Society of Hematology conference [ASH] last year, where again, these allogeneic CARS derived from healthy human donors were able to show clinical activity, both for ALL as well as for non-Hodgkin lymphoma. There are several other clinical trials in development, including for UCART22, UCART123 for ALL. There are many other companies which are developing off the shelf allogeneic CARs, and hopefully we'll see some data may be at this upcoming ASH or in next year meetings as well.

What are the next steps for CAR T-cell use in ALL?

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 CARs to make sure that they are on par with what we are seeing with our autologous CARs. 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 CARs in the early months of therapy. We don't want patients to have 4-5 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.