Among patients with relapsed/refractory large B-cell lymphoma, treatment with cemacabtagene ansegedleucel (cema-cel; formerly ALLO-501/A) was found to demonstrate durable responses, according to data from the single-arm, multicenter, open-label phase 1 ALPHA/ALPHA2 clinical studies which were shared in a news release from Allogene Therapeutics, Inc.
Notably, these studies house the largest dataset of patients with large B-cell lymphoma who were treated with an allogeneic CAR-T cell product, with a minimum of two years of follow-up, which is the longest follow-up to date. Cema-cel, an off-the-shelf CAR-T cell product, demonstrated overall response (ORR) and complete response (CR) rates consistent with those seen in approved autologous CAR-T cell therapies for this patient population after two or more prior lines of systemic therapy. The selected phase 2 regimen had the highest ORR and CR rates of 67% and 58%, respectively.
Glossary
Durability of response (DOR): the length of time a patient experiences a positive response to a treatment, particularly in cancer clinical trials.
Progression-free survival (PFS): the amount of time a patient lives without their cancer growing or spreading, after starting treatment.
Overall survival (OS): the average length of time that people with a disease are alive after starting treatment or being diagnosed.
Overall response rate (ORR): a measure of the percentage of patients whose tumor significantly shrinks or disappears completely after receiving a specific treatment.
Complete response (CR): the context of cancer treatment means the complete disappearance of all detectable signs of cancer.
Minimal residual disease (MRD): a very small number of cancer cells that remain in the body after treatment, often undetectable by standard tests, and can potentially lead to cancer relapse.
The median durability of response (DOR), progression-free survival (PFS) and overall survival (OS) outcomes for patients were 23.1 months, 24 months and not reached, respectively. Among patients receiving the phase 2 regimen, the median DOR was also 23.1 months, while the median OS was not yet reached.
“We tested [cema-cel] out in patients who already had several lines of treatment, and the efficacy results were very intriguing and exciting. What we saw is that 58% of patients had a response, and 42% of patients had a complete response, or a complete disappearance of their lymphoma,” Dr. Frederick L. Locke, trial investigator, explained in an interview with CURE®. “This is comparable to autologous CAR-T, 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 cells.”
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.
As of the data cutoff on Sept. 26, 2024, 87 heavily pretreated patients were treated across the ALPHA/ALPHA2 studies between May 2019 and September 2022. In the most recent news release shared by Allogene Therapeutics, investigators focused on a subset of 33 CD19 CAR-T-naive patients with relapsed/refractory large B-cell lymphoma. These patients received treatment of cema-cel which were manufactured using the process selected for pivotal trials.
“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,” Locke shared in the interview. “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.”
The safety profile of cema-cel was manageable and consistent with that of approved autologous CAR-T therapies. Notably, no dose-limiting toxicities, graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome or high-grade CRS were observed.
The most common treatment-emergent side effects occurring in at least 25% of patients included neutropenia (85%), anemia (67%), thrombocytopenia (58%), infusion-related reactions (58%), fatigue (52%) and pyrexia (49%). Other frequently reported treatment-emergent side effects included nausea (39%), lymphopenia (36%), hypotension (36%), peripheral edema (33%), decreased white blood cell count (30%), cytomegalovirus reactivation (30%), decreased appetite (30%), chills (30%) and hypoxia (27%).
The median time from study enrollment to treatment initiation was two days compared with autologous CAR-T cell products, which typically require wait times exceeding one month due to complex manufacturing and supply chain processes.
“The results [with cema-cel] in patients with large B-cell lymphoma [show] that it can be safely administered and we're able to manage side effects. It certainly can cause the cytokine release syndrome, which is fevers, and are quite common with autologous CAR-T cell therapy, the FDA approved CAR-T cell therapies. With cema-cel, we only saw that CRS in about a quarter of patients, and no severe CRS; we didn't see any neurologic toxicity that we commonly see with autologous CAR T,” Locke explained
Looking to the future, these results have serves as a foundation for the ongoing phase 2 ALPHA3 trial, which will investigate cema-cel as a one-time, off-the-shelf treatment that can be administered immediately upon discovery of minimal residual disease (MRD) following six cycles of treatment, positioning it to become the standard “7th cycle” of frontline treatment available to all eligible patients with MRD, according to the news release.
“These remissions are durable, and they're lasting a long time, several years and more,” Locke concludes. “The use of cema-cel as a potential consolidation after frontline therapy really gives us a chance to keep more patients in remission.”
Transcript was edited for clarity and conciseness.
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