×
A Phase I Study with an Expansion Cohort of the Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Trial of the ECOG-ACRIN Resear...
http://www.bloodjournal.org/content/132/Suppl_1/679

Nov 21st, 2018 - Background: Relapsed/refractory (R/R) Hodgkin lymphoma (HL) remains a significant clinical challenge. We hypothesized that using immune checkpoint blockade to activate the immune cells in the tumor microenvironment, and concurrently targeting tumor cells with the CD30 targeting antibody-drug conjugate brentuximab vedotin (BV) could overcome tumor resistance. E4412 is a Phase 1/2 ECOG-ACRIN spon...

A Phase II Study of Brentuximab Vedotin (BV) in the Treatment of Elderly Hodgkin Lymphoma (HL) Patients at First Relapse or with Primary Refractory Disease — FIL_BVHD01
http://www.bloodjournal.org/content/132/Suppl_1/2920

Nov 21st, 2018 - Older age (≥60 years) has consistently been identified as an independent adverse prognostic factor for Hodgkin lymphoma (HL) survival in population-based studies and clinical trials in the last several decades. Elderly HL patients are significantly underrepresented in clinical trials and have a markedly inferior prognosis compared with younger patients. Brentuximab vedotin (BV) is an antibody-d...

Access to Initial Treatment Was Not the Driving Force of the Survival Disparity By Insurance Status in Follicular Lymphoma — an Analysis of the National Cancer Database (NCDB)
http://www.bloodjournal.org/content/132/Suppl_1/4155

Nov 21st, 2018 - Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. The initial management varies from watchful waiting to a combination of chemoimmunotherapy (CT) and radiation therapy (RT). Goldstein et al. recently reported (Blood, pre-published online, July 24 2018) that FL patients with no insurance or Medicaid had worse OS. We examined whether the survival discrepancy w...

Activation of the Non-Canonical Estrogen Receptor Gper As a Novel Therapeutic Strategy Against Waldenström Macroglobulinemia
http://www.bloodjournal.org/content/132/Suppl_1/1585

Nov 21st, 2018 - Although estrogens have been shown to regulate normal B cell proliferation and differentiation, the impact of estrogen receptor (ER) signaling on B cell malignancies, including Waldenström Macroglobulinemia (WM), remains unexplored. To address this issue, we have analyzed, through preclinical WM models, the druggability either of the classical estrogen receptor ERβ, an emerging target for acute...

An Artificial Intelligence (AI) Approach for Automated Flow Cytometric Diagnosis of B-Cell Lymphoma
http://www.bloodjournal.org/content/132/Suppl_1/2856

Nov 21st, 2018 - Background: Multi-parameter flow cytometry (MFC) data is a diagnostic keystone for hematologic malignancies. Data analysis and interpretation requires resources and expertise, full automation is desired. Combination of automated gating strategies and machine learning on MFC data proved effective in detecting AML cell populations vs normal (Aghaeepour et al., 2013). Aim of our approach was to cr...

Analysis of CAR-T and Immune Cells within the Tumor Micro-Environment of Diffuse Large B-Cell Lymphoma Post CAR-T Treatment By Multiplex Immunofluorescence
http://www.bloodjournal.org/content/132/Suppl_1/678

Nov 21st, 2018 - BACKGROUND: Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that shows efficacy in patients with refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed follicular lymphoma after failure of conventional therapy. However, the exact mechanism of anti-tumor immunity is poorly understood, in part due to ...

CD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies
http://www.bloodjournal.org/content/132/Suppl_1/776

Nov 21st, 2018 - Studying gene expression and clinical outcome data from 136 clinical trials for patients with cancer (~21,000 patients with 26 cancer types), we found CD25 as one of the strongest predictors of poor clinical outcome in patients with B-cell malignancies, but not in other cancer types. This was unexpected because CD25 is known as one of three chains of the IL2 receptor on T-cells and NK-cells. In...

CD30-Chimeric Antigen Receptor (CAR) T Cells for Therapy of Hodgkin Lymphoma (HL)
http://www.bloodjournal.org/content/132/Suppl_1/680

Nov 21st, 2018 - CD19-specific CAR-T cells are highly successful against B-cell non-Hodgkin lymphomas and acute lymphoblastic leukemia but targets for other lymphoproliferative disorders have been harder to define. Almost all HL and some NHL express the CD30 antigen both at diagnosis and relapse, and monoclonal antibodies (mAb) targeting CD30 (e.g. brentuximab) produce objective antitumor responses. However, mA...

CD3-Activating Bi-Specific Antibody Targeting CD19 on B Cells in Mono- and Bi-Valent Format
http://www.bloodjournal.org/content/132/Suppl_1/4169

Nov 21st, 2018 - Immunotherapies targeting B-lineage-specific surface marker CD19 had demonstrated promising clinical results. Two CD19 CAR-T therapies (Kymriah® and Yescarta®) have been approved by FDA to treat patients with B cell malignancies, however, the complicated manufacturing process and low throughput limit its accessibility to more patients, especially in developing countries. The first CD3-activatin...

CD47 Expression Defines the Efficacy of Rituximab in Non-Germinal Center B-Cell (non-GCB) Diffuse Large B-Cell Lymphoma (DLBCL)
http://www.bloodjournal.org/content/132/Suppl_1/2852

Nov 21st, 2018 - CD47 is an immune-checkpoint protein that binds SIRPa on immune cells to deliver an inhibitory "don't eat me" signal. CD47 is a prominent new target in B-cell malignancies, in which CD47 antibody in combination with the CD20 antibody rituximab (R) is explored in clinical trials. Addition of R to CHOP chemotherapy significantly improves survival of patients with DLBCL, but how CD47 expression co...

Atypical Immunophenotype Predicts Worse Prognosis in Adult T-Cell Lymphoma/Leukemia: A Retrospective Study of 63 Caribbean Patients at a New York City Tertiary Center
http://www.bloodjournal.org/content/132/Suppl_1/2906

Nov 21st, 2018 - Background: Adult T-Cell Lymphoma/Leukemia (ATLL) is a rare and aggressive HTLV-1 related peripheral T-cell lymphoma that occurs predominantly in Japan and the Caribbean basin. Acute (A) and lymphomatous (L) subtypes are the most aggressive forms with a median overall survival (OS) of 6-12 months despite chemotherapy. Typical immunophenotype (IP) of ATLL is CD4+/CD8- with strong co-expression o...

Autoimmunity Checkpoints As Therapeutic Targets in B-Cell Malignancies
http://www.bloodjournal.org/content/132/Suppl_1/1587

Nov 21st, 2018 - Concept. Targeted therapy of cancer typically focuses on inhibitors (e.g. tyrosine kinase inhibitors) that suppress oncogenic signaling below a minimum threshold required for survival and proliferation of cancer cells. Acute lymphoblastic leukemia (ALL) and B cell lymphomas originate from various stages of development of B cells, which unlike other cell types are under intense selective pressur...

Characterization of Mechanisms Underlying Acquired Venetoclax-Resistance in Mantle Cell Lymphoma: BDA-366 As a Potential Treatment Option
http://www.bloodjournal.org/content/132/Suppl_1/1580

Nov 21st, 2018 - In many cancers the equilibrium of pro- versus anti-apoptotic BCL-2 proteins is deregulated. BCL-2 inhibitors like Venetoclax (VEN) have been shown to be highly active drugs in BCL-2 dependent cancers like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Despite being highly efficient in cell killing, resistance to VEN can be acquired over time. In addition to understanding th...

Avadomide (CC-122), a Novel Cereblon Modulating Agent, Plus Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma
http://www.bloodjournal.org/content/132/Suppl_1/1602

Nov 21st, 2018 - Introduction:The prognosis is poor for patients with follicular lymphoma (FL) who experience early relapse within 2 years of initial diagnosis and for those who are double refractory to both rituximab and chemotherapy (Casulo et al. J Clin Oncol 2015). Avadomide, a cereblon-modulating agent that promotes degradation of the hematopoietic transcription factors Aiolos and Ikaros, is being examined...

Checkpoint Blockade Therapy May Sensitize Aggressive and Indolent Non-Hodgkin Lymphoma to Subsequent Therapy
http://www.bloodjournal.org/content/132/Suppl_1/93

Nov 21st, 2018 - Background: Outcomes to salvage therapy for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) are suboptimal. Checkpoint blockade therapy (CBT) has been explored in the relapsed/refractory (R/R) NHL population, but response rates to single agent CBT therapy are modest. To date, there is no literature on whether treatment with CBT may sensitize NHL patients to subsequent therapy...

Checkpoint Blockade Therapy May Sensitize Hodgkin Lymphoma to Subsequent Therapy
http://www.bloodjournal.org/content/132/Suppl_1/1626

Nov 21st, 2018 - Background: Relapsed or refractory (R/R) Hodgkin lymphoma (HL) remains a significant clinical problem. Recently checkpoint blockade therapy (CBT) has shown striking activity in this setting, but the complete response (CR) rate is modest. Patients who relapse after CBT have limited therapeutic options. A prior, retrospective study showed that after anti-PD-1 therapy the objective response rate t...

Enhanced Expression of FGF Signaling in Primary Central Nervous System Lymphoma
http://www.bloodjournal.org/content/132/Suppl_1/2847

Nov 21st, 2018 - Introduction: Primary central nervous system lymphoma (PCNSL) is a rare intracranial lymphoma that accounts for less than 1% of all non-Hodgkins lymphomas and 3% of all brain tumors. Histopathologically, approximately 90% of PCNSL cases are categorized as a diffuse large B-Cell lymphoma (DLBCL). DLBCL malignancies are subdivided by Cell of Origin (COO), with the vast majority of PCNSL categoriz...

Baseline PET-Derived Metabolic Tumor Volume Metrics Did Not Predict Outcomes in Follicular Lymphoma Patients Treated with First-Line Immunochemotherapy and Antibody Maintenance in the Phase III GAL...
http://www.bloodjournal.org/content/132/Suppl_1/2882

Nov 21st, 2018 - Introduction: Evidence suggests that baseline 18fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography-derived parameters, such as metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax), may predict progression-free survival (PFS) in patients (pts) with follicular lymphoma (FL) treated with first-line R-CHOP immunochemotherapy. However, data from pt...

Epiproteomic Landscape and Histone Code of Cutaneous T-Cell Lymphoma/Sézary Syndrome
http://www.bloodjournal.org/content/132/Suppl_1/780

Nov 21st, 2018 - Background: The genetic basis and the genome-wide abnormalities underlying most forms of cancer are being comprehensively annotated in many human malignancies. However, the contribution of epigenetic aberrations, particularly the post-translational modifications (PTM) of histone tails has not been investigated. This is largely due to lack of approaches to comprehensively interrogate the status ...

Estimation of the Resource Utilization and Costs of Cytokine Release Syndrome Observed in the Transcend-NHL Clinical Trial: A Micro-Costing Study
http://www.bloodjournal.org/content/132/Suppl_1/319

Nov 21st, 2018 - INTRODUCTION: Information on the differential resources and costs associated with managing treatment-related adverse events (TRAEs) from chimeric antigen receptor T-cell (CAR T) therapies, including cytokine release syndrome (CRS), have not been estimated and may differ by therapy. Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in a defined...