Clinical activity of P-BCMA-ALLO1, a B-cell maturation antigen (BCMA) targeted allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed refractory multiple myeloma (RRMM) patients (pts) following progression on prior BCMA targeting therapy

P-BCMA-ALLO1 is a novel investigational BCMA-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor T-cell (CAR-T) therapy manufactured from healthy donor T-cells and available off-the-shelf. The findings presented at the AACR 2024 demonstrated that around 60% of patients (3 out of 5) with RRMM, who had advanced after receiving BCMA-targeted therapy, showed clinical improvements with P-BCMA-ALLO1. Furthermore, this investigational therapy exhibited favorable tolerability. Moreover, These latest findings further support the potential of the experimental off-the-shelf allogeneic CAR-T therapy as a viable option for a wider spectrum of multiple myeloma patients, particularly those with relapsed/refractory disease whose cancer progressed after previous BCMA-targeted therapy—a population with the most urgent medical need in this setting.

KOL insights

“Multiple myeloma remains incurable, and patients often relapse, despite initial high response rates with BCMA-targeted immunotherapies, including autologous CAR-T therapies.”–Expert Opinion.

“New treatment options are urgently needed for these patients, which is why I’m encouraged by these impressive Phase 1 subgroup results, which may be the first report of an allogeneic CAR-T therapy showing clinical activity in heavily pretreated patients whose myeloma has progressed after multiple BCMA-targeted immunotherapies.” –Expert Opinion.

Conclusion

While BCMA CAR T therapies have demonstrated significant efficacy, the prospect of patients potentially discontinuing all treatments after a single CAR T infusion is highly promising. Nonetheless, access to myeloma CAR T remains restricted, and the lengthy manufacturing process hampers their utility in patients requiring immediate treatment. However, these Phase 1 subgroup findings are encouraging, possibly marking the inaugural instance of an allogeneic CAR-T therapy exhibiting clinical efficacy in heavily treated patients with progressive myeloma following multiple BCMA-targeted immunotherapies. Apart from that, the company is actively investigating the most effective lymphodepletion regimen for CAR-T therapy in solid tumors and is leveraging these insights directly into the P-MUC1C-ALLO1 trial. The aim is to replicate the success observed in myeloma for solid tumors. Lastly, the company anticipates sharing comprehensive datasets on both the BCMA and MUC1-C programs in the second half of 2024.