Researchers found a biomarker that, if confirmed, could be used to identify which people with chronic lymphocytic leukemia would benefit from CAR T-cell therapy.

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The efficacy of autologous (αβ) T-cell–based treatment strategies in chronic lymphocytic leukemia (CLL) has been modest. The V9V2-T cell subset consists of cytotoxic T lymphocytes with potent antilymphoma activity via a major histocompatibility complex–independent mechanism. We studied whether V9V2-T cells can be exploited as autologous effector lymphocytes in CLL. Healthy control V9V2-T cells were activated by and had potent cytolytic activity against CLL cells. However, CLL-derived V9V2-T cells proved dysfunctional with respect to effector cytokine production and degranulation, despite an increased…

Source: BloodCategory: Hematology Authors: Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research

Conclusions: Our data demonstrate that significant venetoclax-induced cell death at clinically relevant drug concentrations is limited to the B-cell subset and that BCL-2 inhibition is not detrimental to survival or activation of NK- or T-cell subsets. Importantly, preclinical mouse models confirm the combinability of BCL-2 and PD-L1 inhibitors. These data support the combined use of venetoclax and cancer immunotherapy agents in the treatment of patients with hematologic and solid tumor malignancies.FigureDisclosuresLasater: Genentech Inc: Employment. Do: Genentech Inc: Employment. Burton: Genentech Inc: Employment. Li: Ge…

Source: BloodCategory: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster I Source Type: research

Conclusion. The clinical spectrum of hematologic irAE is wide and dominated by neutropenia, hemolytic anemia and immune thrombocytopenia. Aplastic anemia is rarer and present as a life-threatening condition. The prevalence of grade ≥2 hematologic irAEs following anti-PD(L)1 was 0.54%. The recurrence rate after rechallenge was 50%. Further prospective investigations are warranted to better detect and manage hematologic immune-related adverse events.DisclosuresHerbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Maerevoet: abbvie: Membership on an entity’…

Source: BloodCategory: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster II Source Type: research

Conclusions: Our data suggest that pharmacologic targeting of NAE preserves T-cell cytotoxic function and may enhance anti-tumor immunity in CLL. Combined with our earlier reports that targeting NAE kills CLL cells under lymph node-mimicking conditions, these data provide a strong rationale for continued investigation of pevonedistat in CLL and lymphoid malignancies.DisclosuresSpurgeon: Bristol Myers Squibb: Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Oncternal: Research Funding; Acerta: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy, Researc…

Source: BloodCategory: Hematology Authors: Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster II Source Type: research

In this study, we used a mass spectrometry-based approach to identify naturally presented, CML-associated peptides in primary CML samples (HLA class I, n=21, 11,945 peptides, 5,478 source proteins; class II, n=20, 5,991 peptides, 1,302 proteins). Comparative HLA peptidome profiling using a comprehensive dataset of various benign tissues (e.g. blood, bone marrow, spleen, and lung) revealed frequently presented and strictly CML-associated antigens. In detail, the benign tissue dataset comprises hematological benign samples (class I, n=108, 51,233 peptides, 11,437 proteins; class II, n=88, 42,753 peptides, 4,877 proteins) and…

Source: BloodCategory: Hematology Authors: Tags: 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Chimeric antigen receptor (CAR)-modified T-cell therapy targeting CD19 induces high response rates in patients with relapsed or refractory B-cell lymphomas. However, about 60% of patients experience primary or secondary resistance after CD19-targeted CAR T-cell therapy and a major of cause of failure appears to be due to loss of CD19 expression on the tumor. Therefore, novel targets for adoptive T-cell therapeutic approaches are needed to further improve clinical outcome in these patients.T-cell leukemia/lymphoma antigen1 (TCL1) is an oncoprotein that is overexpressed in multiple B-cell malignancies including follicular ly…

Source: BloodCategory: Hematology Authors: Tags: 801. Gene Therapy and Transfer: Poster II Source Type: research

Despite the remarkable outcomes and recent FDA approval of CD19 directed chimeric antigen receptor T (CART19) cell therapy in B cell malignancies, the durable responses in diffuse large B cell lymphoma are less than 40% and CART activity in chronic lymphocytic leukemia (CLL) is further limited. This is thought to be related to loss of CART persistence, poor trafficking to lymph nodes and inhibition by the leukemic microenvironment. Therefore, strategies to enhance CART cell function to overcome these limitations are needed. Recent studies have shown that abnormal expression of the receptor tyrosine kinase (RTK) AXL is asso…

Source: BloodCategory: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Pre-clinical T and NK Cell Immunotherapies Source Type: research

We report adverse events that occurred or persisted beyond 90 days after the last CAR-T cell infusion, excluding events related to disease progression.Median age at CAR-T cell infusion was 60 years (range, 34-73). There were 42 (71%) pts with NHL and 17 (29%) with CLL. The median number of prior lines of treatment was 4 (range, 1-8). 23 (39%) pts had received prior autologous (auto) hematopoietic cell transplantation (HCT), and 9 (15%) pts had received prior allogeneic (allo) HCT. 35 (59%) pts received one CAR-T cell infusion, 22 (37%) pts received 2 infusions, and 2 (3%) pts received 3 infusions. 3 (5%) pts received a max…

Source: BloodCategory: Hematology Authors: Tags: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials: Immunotherapy Source Type: research

ConclusionThis is the first report describing a skewed mitochondrial metabolic profile in CLL CD8+ T cells prior to stimulation, which is maintained after stimulation and is then accompanied by impaired glucose uptake. Decreased mitochondrial fitness correlates with impaired CAR-T cell persistence and poor responses. Therefore, boosting mitochondrial biogenesis in T cells in CLL might improve the efficacy of CAR-T cell therapy and other emerging cellular immunotherapies.DisclosuresFraietta: Novartis: Patents &Royalties: WO/2015/157252, WO/2016/164580, WO/2017/049166. Eldering: Celgene: Research Funding. Levin: Celgene:…

Source: BloodCategory: Hematology Authors: Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Overcoming Immunodeficiency in CLL Source Type: research

The targeted therapy ibrutinib inhibits B cell receptor signaling (BTK inhibitor) and has yielded high response rates and durable remissions in patients with chronic lymphocytic leukemia (CLL). However, it is widely believed that the addition of immune therapies to targeted drugs will be required to activate anti-tumor immunity and work towards curative therapy. Identifying effective combinations of targeted drugs and/or standard chemotherapy with immunotherapy is a priority research area and particularly relevant for CLL, as patients’ T cells have been shown to exhibit profound tolerance/exhaustion and notably, no activit…

Source: BloodCategory: Hematology Authors: Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Overcoming Immunodeficiency in CLL Source Type: research



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