627. Aggressive Lymphoma (Diffuse Large B-Cell & Other Aggressive B-Cell NHL)- Retrospective/Observational Studies: Predicting Efficacy & Safety of CAR-T cells & Checkpoint Blockade


Patient Characteristics and Pre-Infusion Biomarkers of Inflammation Correlate with Clinical Outcomes after Treatment with the Defined Composition, CD19-Targeted CAR T Cell Product, JCAR017

Tanya Siddiqi, et al.

The authors of the study conclude:

Preliminary analysis has identified baseline patient characteristics, including inflammatory state and high tumor burden prior to treatment, as a means to identify patients at risk for increased toxicity following administration of JCAR017. Low tumor burden and low inflammatory state appear associated with improved toxicity profile and better durability of response. These preliminary data suggest that treating pts earlier in their course of therapy, or using a panel of clinical and laboratory biomarkers to risk stratify patients for potential early intervention, is feasible and may mitigate risk of toxicity and potentially improve durability of response.



Predicting Clinical Response and Safety of JCAR017 in B-NHL Patients: Potential Importance of Tumor Microenvironment Biomarkers and CAR T-Cell Tumor Infiltration

Christina Swanson, et al.

The authors of the study conclude:

The state of the tumor microenvironment prior to treatment may impact the efficacy of CAR T cell therapy. This initial analysis suggests durable response at month 3 is associated with higher levels of CD4+ cells in pretreatment tumors. Following JCAR017 therapy, CAR T cells, both CD4+ and CD8+, infiltrated the tumor and adjacent tissue. BOR was associated with an increase in CAR T cells. Increasing levels of CD8+ cells in the tumor were associated with increases in IDO and PD-L1, suggesting that therapies targeting these pathways may enhance JCAR017 activity. Detailed analyses are ongoing to examine additional associations of tumor burden, T cell infiltration, and immunosuppressive factor expression with clinical efficacy, PK and safety, and will be presented.



High Expression of Programmed Death-Ligand 1 (PD-L1) Correlates with Macrophage Gene Expression and Is Associated with Prolonged Progression-Free Survival (PFS) in Patients (pts) with First-Line (1L) Diffuse Large B-Cell Lymphoma (DLBCL)

Ronald McCord, et al.

The authors of the study conclude:

In 1L DLBCL, most pts expressed PD-L1 on immune cells with myeloid/dendritic morphology, potentially reflecting activated macrophages primed for ADCP and supportive of the correlation between high PD-L1 expression and improved clinical outcomes among pts treated with immunochemotherapy. In the context of anti-CD20, the biology of PD-L1 expression on macrophages and the impact of PD-L1/PD-1 blockade on ADCP merit further study.



Clinical Characteristics and Outcome of Diffuse Large B-Cell Lymphoma with 9p24.1 Copy Number Alterations

Yucai Wang, et al.

The authors of the study conclude:

9p24.1 CNA was present in 8% of de novo DLBCL patients and was associated with increased expression of PD-L1. Patients with 9p24.1 CNA were younger compared to those without. Presence of 9p24.1 CNA was associated with statistically significant superior EFS. While immune checkpoint inhibitors targeting PD-1/PD-L1 are being evaluated in DLBCL in clinical trials, whether 9p24.1 CNA is a biomarker predicting favorable response and treatment outcome should be further examined.



Clinical Significance of PD-1 and PD-L1 Expression and Ongoing Interaction in the Tumor Microenvironment in Diffuse Large B Cell Lymphoma (DLBCL) Treated with R-CHOP

Zijun Yidan Xu-Monette, et al.

The authors of the study conclude:

PD-1 expression in T cells and lack of tumor-infiltrating CD3+ T cells are associated with significantly poorer survival of DLBCL patients. In addition, our data suggest that PD-1 can be a prognostic marker independent of PD-1/PD-L1 co-localization, and that PD-L1 has other PD-1-independent inhibitory functions. These results demonstrate the importance of both T-cell influx and antitumor function in prolonging the survival of DLBCL patients, and provide rationales for PD-1 blockade and immunotherapies activating T cell-mediated immune responses in DLBCL.



Increased Incidence of Autoimmune and Infectious Diseases Among a Large Group of Diffuse Large B-Cell Lymphoma (DLBCL) Survivors: A Population-Based Study

Tanaya Shree, et al.

The authors of the study conclude:

These findings in a large, population-based study suggest that compared to survivors of other common cancers, DLBCL survivors experience excess immune-related conditions, some expected (such as autoimmune hemolytic anemia and thrombocytopenia) and others unexpected (such as fungal and viral pneumonias and diffuse connective tissue diseases). This information suggests possible lasting effects of lymphoma and its treatments on the immune system and motivates further examination of immune function in DLBCL survivors.