Allogene Therapeutics announced positive results from its Phase 1 ALPHA and ALPHA2 clinical trials of cema-cel, an allogeneic CAR T therapy for relapsed/refractory large B-cell lymphoma (LBCL). The therapy demonstrated comparable efficacy to approved autologous CD19 CAR T treatments, with a manageable safety profile and rapid treatment initiation. Data from the trials, published in the Journal of Clinical Oncology, represent the largest and longest follow-up dataset for an allogeneic CAR T product in LBCL patients.
These findings are potentially groundbreaking for lymphoma treatment. The demonstrated efficacy and safety of cema-cel, along with its “off-the-shelf” availability, could significantly expand access to CAR T therapy for LBCL patients. The rapid two-day treatment initiation offers a substantial advantage over autologous CAR T therapies, which often involve lengthy manufacturing processes. The positive results in patients with low disease burden suggest potential for earlier intervention and improved outcomes.
The combined ALPHA/ALPHA2 trials enrolled 87 patients with relapsed/refractory non-Hodgkin lymphoma. For the 33 LBCL patients who received the pivotal study regimen, the overall response rate was 67%, with a complete response rate of 58%. The median duration of response for patients achieving complete remission was 23.1 months, with median overall survival not yet reached. Importantly, no graft-versus-host disease, ICANS, or high-grade cytokine release syndrome were observed. In a subset of patients with low disease burden, the complete response rate was remarkably high, reaching 100% in some cases.
These promising results support the ongoing ALPHA3 trial, which is investigating cema-cel as a first-line consolidation therapy for LBCL patients who are in remission but have minimal residual disease (MRD). The ALPHA3 trial aims to intervene early in these high-risk patients, potentially preventing relapse and reshaping the standard of care for LBCL. If successful, cema-cel could become a standard component of frontline LBCL treatment, administered shortly after initial chemoimmunotherapy in MRD-positive patients. This represents a paradigm shift from the current “watch and wait” approach, offering a proactive strategy to eliminate residual disease and improve long-term outcomes.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
