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<p>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 T<sub>SCM</sub>-predominant allogeneic CAR-T therapy targeting BCMA in heavily pretreated relapsed/refractory multiple myeloma. Preclinical analyses reveal a strong correlation between CD8<sup>+</sup> T<sub>SCM</sub> 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 (T<sub>max</sub>) was 10 days post-infusion. Consistent with preclinical findings, CAR-T cell expansion is accompanied by differentiation from a predominantly T<sub>SCM</sub> phenotype to a T<sub>EM</sub>/T<sub>EFF</sub> phenotype, with trafficking and persistence observed in bone marrow. These data suggest that a T<sub>SCM</sub> cellular phenotype may offer significant advantages in efficacy, safety, and cellular persistence in the context of allogeneic CAR-T therapy. Clinical trial: NCT04960579</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月24日

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  • 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,
  • Devon J. Shedlock

摘要

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