704. Immunotherapies I


Safety and Anti-Tumor Activity of CD5 CAR T-Cells in Patients with Relapsed/Refractory T-Cell Malignancies

LaQuisa C. Hill, et al. 

Conclusion cited from the abstract: 

These results demonstrate that CD5 CAR T cells are safe and can induce clinical responses in heavily treated patients with r/r CD5+ T-ALL and T-NHL without inducing complete T-cell aplasia. Importantly, elimination of malignant T cells by CD5 CAR T cells may allow previously ineligible patients to proceed to HSCT.




Donor-Derived CD19 CAR Cytokine Induced Killer (CIK) Cells Engineered with Sleeping Beauty Transposon for Relapsed B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Chiara F Magnani et al. 

Conclusion cited from the abstract: 

Our ongoing phase I/II trial demonstrates that SB-engineered CARCIK-CD19 cells are able to expand and persist in pediatric and adult B-ALL patients relapsed after HSCT, with important implications for a non-viral technology. These encouraging results prompted us to expand our study.



Factors Associated with Response, CAR-T Cell In Vivo Expansion, and Progression-Free Survival after Repeat Infusions of CD19 CAR-T Cells

Evandro D. Bezerra, et al. 

Conclusion cited from the abstract: Our findings suggest outcomes after second infusions of CD19 CAR-T cells might be improved with high-intensity CyFlu lymphodepletion prior to CART1 and by increasing the CAR-T cell dose at the time of CART2.




Multiplexed Immunofluorescence (IF) Analysis and Gene Expression Profiling of Biopsies from Patients with Relapsed/Refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL) Treated with Lisocabtagene Maraleucel (liso-cel) in Transcend NHL 001 Reveal Patterns of Immune Infiltration Associated with Durable Response

David J. Reiss, et al. 

Conclusion cited from the abstract: Overall, these data suggest that increased infiltration of tumor-specific CAR T cells upon initial treatment with liso-cel helped establish an active immune response, and that recruitment of additional functional endogenous (particularly CD4+) T cells correlated with durable response. Higher numbers of activated/functional T cells and lower numbers of macrophages prior to treatment also correlated with durable response to liso-cel. Thus, tumors in responders may already have had a baseline TME in which T cells could infiltrate and respond to antigen. This may have promoted the success of CAR T cell entry into tumors and the subsequent recruitment and activation of endogenous lymphocytes that support their function.



CD19-Loss with Preservation of Other B Cell Lineage Features in Patients with Large B Cell Lymphoma Who Relapsed Post–Axi-Cel

Sattva S Neelapu, et al. 

Conclusion cited from the abstract: 

In this cohort of patients relapsing after axi-cel, loss of CD19 expression was common by IHC as compared to pretreatment, likely due to alternative splicing and selection of variants devoid of target epitope. Additionally, the data showed that expression of alternate B cell lineage antigens was largely preserved. In particular, CD20 cell surface expression was strong in most tumors despite prior rituximab-based treatments. Altogether, these data point to strategies to improve efficacy of anti-CD19 CAR T cell products through co-targeting or sequential targeting of alternate B cell antigens.




Efficacy and Safety of Fully Human Bcma CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase Bcma Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma

Andrew J. Cowan, et al. 

Conclusion cited from the abstract: Although BCMA CAR T cell therapy has demonstrated potent anti-tumor efficacy in multiple myeloma, a significant proportion of patients relapse. The mechanism of myeloma recrudescence requires further study, however BCMA antigen loss has been observed after CAR T cell therapy and is a putative pathway for tumor escape. In this study we demonstrate that gamma secretase inhibition with JSMD194 routinely increases BCMA surface density on myeloma cells in treated patients and reduces soluble BCMA. The combination of a gamma secretase inhibitor with BCMA CAR T cells leads to rapid responses including in patients that have failed prior BCMA targeted therapy. These responses are achieved with low CAR T cell doses. Longer follow up is required to determine if the durability of response is improved.



Impact of Lisocabtagene Maraleucel (liso-cel) Treatment on Health-Related Quality of Life and Health Utility in Patients (pts) with Relapsed/Refractory (R/R) Aggressive B Cell Non-Hodgkin Lymphoma (NHL): Transcend NHL 001

Donald L. Patrick, Annette Powers, Monika Parisi, Yeonhee Kim, et al.

In TRANSCEND NHL 001, pts in the DLBCL cohort experienced an improvement in HRQoL and health utility through Month 12, though some reported a detriment at Month 1. Reduced fatigue and pain symptom burden through Month 12 after liso-cel infusion was also reported. Overall, in spite of the limitations inherent in the study, a notable proportion of pts demonstrated clinically meaningful improvements at Months 6 and 12.

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