Myeloma: Therapy, excluding Transplantation: Immunotherapy
1009 Tandem Autologous Transplantation and Combined Infusion of CD19 and Bcma-Specific Chimeric Antigen Receptor T Cells for High-Risk MM: Initial Safety and Efficacy Report from a Clinical Pilot Study
Xiaolan Shi, et al.
The Abstract concludes: Tandem autologous transplantation and combined infusion of CART-19 and CART-BCMA cells could be another choice of consolidation treatment for high-risk MM patients. Toxicities to date including CRS and organ function impairment seemed to be mild and reversible. It is worthy of further study to compare DFS, OS between single autologous transplantation and tandem transplantation with CART therapy. Immune environment in high-risk patients with multiple myelomaI remodeled by auto-HSCT may contribute to a more rapid expansion of CART cells than that in RRMM patients, suggesting that the extent of CART expansion depends more than tumor burden.
1010 Treatment with AMG 420, an Anti-B-Cell Maturation Antigen (BCMA) Bispecific T-Cell Engager (BiTEÂ®) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase I Dose Escalation Study
Max S. Topp, et al.
The Abstract concludes: In this FIH study, AMG 420, a short half-life BiTE® targeting BCMA, showed encouraging evidence of activity in patients with R/R multiple myeloma. During dose escalation, all 3 patients dosed with 400 µg/d had MRD-negative CRs, with 2 more responders in the dose confirmation cohort to date; 3 patients at lower doses also attained CRs. No major toxicities were observed up to 400 µg/d, which is a recommended dose for further investigation; DLTs at 800 µg/d were CRS and PPN.
Damian J. Green, et al.
The Abstract concludes: BCMA CAR T cells harboring a fully human scFv with a defined composition of CD4+:CD8+ T cells were well tolerated and potent, demonstrating complete objective responses in heavily pretreated high-risk MM at total cell doses as low as 5 x 107. Next-generation sequencing and multiparameter high sensitivity flow cytometry studies to evaluate for minimal residual disease are ongoing. Peak expansion levels and persistence of the CAR T cells are being monitored with early findings suggesting an absence of transgene product immunogenicity.
Tara Gregory, et al.
The Abstract concludes: In conclusion, current clinical trial data in patients with r/r MM support preclinical findings that the novel design of P-BCMA-101 can produce significant efficacy, comparing favorably with other anti-BCMA CAR-T products at similar doses, with notably less CRS and no neurotoxicity, consistent with the hypothesis of an improved therapeutic index.
Chunrui Li, et al.
The Abstract concludes: That BCMA-CAR T cell therapy is feasible, safe, and mediates potent anti-tumor activity in relapsed/refractory Multiple Myeloma. All toxicities were reversible Our results should encourage additional development of CAR T-cell therapies for other plasma cell malignancies such as plasma cell leukemia and POEMS.
Premal Lulla, et al.
The Abstract concludes: Notably, no patient, including the complete responder, had infusion-related systemic- or neuro-toxicity. Thus, autologous multiTAA-targeted T cells directed to PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin can be safely administered to patients with MM, in whom they can subsequently be detected long-term in peripheral blood and marrow, and where they produce sustained tumor responses including CR. It will be of interest to discover whether larger or more frequent doses of these T cells can produce further benefit with maintained safety.