Dr. Frederick L. Locke serves as chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and Research Institute, in Tampa, Florida, also explained the mechanism of action of the agent.

Dr. Frederick L. Locke

Dr. Frederick L. Locke sat down with CURE® to discuss treatment with cema-cel in the ALPHA/ALPHA2 study for relapsed/refractory large B-cell lymphoma.

Breaking Down The Results of The ALPHA/ALPHA2 Study in Large B-Cell Lymphoma

Cemacabtagene ansegedleucel (cema-cel; formerly ALLO-501/A) is an off-the-shelf allogeneic CAR-T cell therapy, Dr. Frederick L. Locke described in an interview with CURE®, saying that treatment with the CAR-T product demonstrated responses in patients with relapsed/refractory large B-cell lymphoma.

These responses were recorded in findings from the phase 1 ALPHA/ALPHA2 study, which were shared in a press release from Allogene Therapeutics, Inc. Among heavily pretreated patients, the selected phase 2 regimen achieved an overall response rate of 67% and a complete response rate of 58%, with a median duration of response of 23.1 months, Locke explained. Moreover, the safety profile was manageable, with no severe cytokine release syndrome (CRS) or neurotoxicity observed.

Locke serves as an investigator of cema-cel, as well as the chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and Research Institute, in Tampa, Florida. In the interview with CURE, he expanded on the key takeaways derived from the trial. 

Read more from Locke and learn more about cema-cel here.

The ALPHA/ALPHA2 trial is a phase one, single-arm clinical trial that which tests the safety and efficacy of cema-cel in large B-cell and relapsed/refractory non-Hodgkin lymphoma. The results in patients with large B-cell lymphoma [show] that it can be safely administered and [oncologists are] able to manage side effects. It certainly can cause cytokine release syndrome [CRS] — which is fevers — which are common with autologous CAR-T cell therapy, the FDA-approved CAR-T cell therapies. With cema-cel we only saw CRS in about a quarter of patients, and no severe CRS [was reported]. We didn't see any neurologic toxicity that we commonly see with autologous CAR-T.

We tested [cema-cel] out in patients who had already [been treated with] several lines of treatment and the efficacy results were very intriguing and exciting. We saw that 58% of patients had a response, and 42% of patients had a complete response, or complete disappearance of their lymphoma on the ALPHA/ALPHA2 studies. This this is comparable with autologous CAR-T cell [therapy], but because it's allogeneic, we can give the cells almost immediately to our patients. We don't have to wait a month for the CAR-T cells to be made. [Therefore], it has some advantages over autologous CAR-T.

Transcript was edited for clarity and conciseness.

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Cemacabtagene ansegedleucel (cema-cel) is an allogeneic CAR-T cell therapy showing promise in treating relapsed/refractory large B-cell lymphoma. In the phase 1 ALPHA/ALPHA2 study, cema-cel achieved a 67% overall response rate and a 58% complete response rate among heavily pretreated patients, with a median response duration of 23.1 months. The safety profile was favorable, with no severe cytokine release syndrome or neurotoxicity observed. Cema-cel offers advantages over autologous CAR-T therapies, including immediate availability for patients without the need for cell manufacturing delays.

Dr. Frederick L. Locke sat down with CURE® to discuss treatment with cema-cel in the ALPHA/ALPHA2 studies for relapsed/refractory large B-cell lymphoma.

Treatment with cemacabtagene ansegedleucel demonstrated responses in patients with relapsed or treatment-resistant large B-cell lymphoma.

Off-The-Shelf CAR T Therapy Elicits Responses in Large B-Cell Lymphoma

Treatment with cemacabtagene ansegedleucel (cema-cel) demonstrated responses in patients with relapsed or treatment-resistant large B-cell lymphoma, according to information from a phase 1 trial which were shared in a news release from Allogene Therapeutics, Inc; data on the investigation were also published in the Journal of Clinical Oncology.

The "off-the-shelf" CAR T-cell therapy elicited an overall response rate of 58% and complete response rate of 42% in patients enrolled on the study, and many patients who achieved complete remission remained cancer-free for over two years; the median overall survival has not yet been reached.

Overall response rate: Patients who responded partially or completely to treatment.

Overall survival: The time a patient lives, regardless of disease status.

®, Dr. Frederick L. Locke, expanded on how cema-cel compares with currently available CAR T-cell therapies in terms of effectiveness and safety for patients with relapsed/refractory large B-cell lymphoma. Locke, who serves as chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and Research Institute, in Tampa, Florida, also explained the mechanism of action of the agent.

Cema-cel is an allogeneic CAR-T cell therapy, so it's coming from healthy donors, and that's different than the CAR-T cell therapies that are currently FDA approved. With the FDA-approved CAR-T cell therapies for large B-cell lymphoma, the T cells are coming from the patient; the T cells are removed from the patient's blood. T cells recognize infected cells or foreign things, and with autologous CAR-T cell therapy, a gene is put in the patient's own cells to reprogram them against CD-19, which is a protein on the surface of the cancerous B cells. Then, the cells are infused back into the patient, where they know where to go and what to do. They then attack and destroy the cancerous B cells.

With cema-cel, it's the same concept of reprogramming using the chimeric antigen receptor [CAR], but instead of using the patient's own T cells, we use donor cells. Those donor cells not only express the CAR against CD-19, but they also have gene editing to remove several genes and proteins within the donor cells. One is CD-52 which is simply a cell surface protein on many immune cells in the body, and that allows us to use a monoclonal antibody to reduce the normal immune cells transiently. This lets that allogeneic donor cells get in and expand. Also, something called the TRAC locus removes the T cell receptor from the donor cells. That T cell receptor is what tells the T cell where to go and what to do. By removing that from the donor cells, we prevent the donor cells from recognizing the patient's body as abnormal or foreign, so we don't have graft-versus-host disease.

Dr. Frederick L. Locke

Breaking Down The Results of The ALPHA/ALPHA2 Study in Large B-Cell Lymphoma

Off-The-Shelf CAR T Therapy Elicits Responses in Large B-Cell Lymphoma

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