TSCM-predominant allogeneic anti-BCMA CAR-T therapy for relapsed/refractory multiple myeloma: preclinical characterization and interim results from a phase 1 trial

Hubert Tseng, Bhagirathbhai Dholaria, Stacey A. Cranert, Maximilian Richter, Karl S. Marquez, Benjamin S. Cho, Andrew Bacong, Katherine McArthur, Jeff D. Eskew, Joanne McCaigue, Sabrina Haag, Aly Krasny, Brian Solimine, Michael J. Coffey, Aimee Loyola, Jasmine Kwong, Leyla Shune, Andrew Kin, Caitlin L. Costello, Mehmet H. Kocoglu, Aravind Ramakrishnan, Hamid Namini, Christopher E. Martin, Rajesh Belani, Julia Coronella and Devon J. Shedlock ()
Additional contact information
Hubert Tseng: Inc, Poseida Therapeutics
Bhagirathbhai Dholaria: Vanderbilt University Medical Center, Department of Medicine, Department of Hematology and Oncology
Stacey A. Cranert: Inc, Poseida Therapeutics
Maximilian Richter: Inc, Poseida Therapeutics
Karl S. Marquez: Inc, Poseida Therapeutics
Benjamin S. Cho: Inc, Poseida Therapeutics
Andrew Bacong: Inc, Poseida Therapeutics
Katherine McArthur: Inc, Poseida Therapeutics
Jeff D. Eskew: Inc, Poseida Therapeutics
Joanne McCaigue: Inc, Poseida Therapeutics
Sabrina Haag: Inc, Poseida Therapeutics
Aly Krasny: Inc, Poseida Therapeutics
Brian Solimine: Inc, Poseida Therapeutics
Michael J. Coffey: Inc, Poseida Therapeutics
Aimee Loyola: Inc, Poseida Therapeutics
Jasmine Kwong: Inc, Poseida Therapeutics
Leyla Shune: Westwood, Division of Hematological Malignancies and Cellular Therapeutics, University of Kansas Medical Center
Andrew Kin: Wayne State University, Karmanos Cancer Institute
Caitlin L. Costello: University of California San Diego, Moores Cancer Center
Mehmet H. Kocoglu: University of Maryland Medical Center, Marlene and Stewart Greenebaum Comprehensive Cancer Center
Aravind Ramakrishnan: St. David’s South Austin Medical Center, Sarah Cannon Transplant and Cellular Therapy Program
Hamid Namini: Inc, Poseida Therapeutics
Christopher E. Martin: Inc, Poseida Therapeutics
Rajesh Belani: Inc, Poseida Therapeutics
Julia Coronella: Inc, Poseida Therapeutics
Devon J. Shedlock: Inc, Poseida Therapeutics

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Autologous CAR-T therapies targeting B-cell maturation antigen (BCMA) in relapsed/refractory multiple myeloma (RRMM) have demonstrated therapeutic clinical responses. Here, we present the characterization and interim Phase I data for P-BCMA-ALLO1, a TSCM-predominant allogeneic CAR-T therapy targeting BCMA in heavily pretreated relapsed/refractory multiple myeloma. Preclinical analyses reveal a strong correlation between CD8+ TSCM phenotype and in vivo potency in mouse xenograft models. In early clinical data (NCT04960579), among the 11 of 33 evaluable patients who received enhanced lymphodepletion, 82% (9/11) responded, with 63.6% (7/11) achieving very good partial response (VGPR) or better. All patients started therapy a median of 1 day after enrollment, with every patient receiving P-BCMA-ALLO1 infusion, and resulting in a 100% intent-to-treat (ITT) rate with no use of bridging therapy. CRS was reported in 21.2% (7/33) across all cohorts, all grade ≤2. The median time to peak CAR-T cell expansion (Tmax) was 10 days post-infusion. Consistent with preclinical findings, CAR-T cell expansion is accompanied by differentiation from a predominantly TSCM phenotype to a TEM/TEFF phenotype, with trafficking and persistence observed in bone marrow. These data suggest that a TSCM cellular phenotype may offer significant advantages in efficacy, safety, and cellular persistence in the context of allogeneic CAR-T therapy. Clinical trial: NCT04960579

Date: 2025
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DOI: 10.1038/s41467-025-65267-0

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