Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells

We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5 –3.27 × 107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12 –55%) at 2 months: 2 had complete response lasting 3 and 9 months. Circulating donor NK cells persisted for at least 7 days after infusion at the level 0.6–16 donor NK cells/µl or 0.35–90% of total CD56 cells. Responding patients had lower levels of circulating host-derived Tregs (17 ± 4 vs. 307 ± 152 cells/µL;p = 0.008) and myeloid-derived suppressor cells at baseline (6.6 ± 1.4% vs. 13.0 ± 2.7%;p = 0.06) than non-responding patients. Lower circulating Tregs correlated with low serum levels of IL-10 (R2 = 0.64;p 
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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A promising and expensive type of immunotherapy, called CAR T-cell therapy, is now covered by Medicare. This news may affect mesothelioma patients in the future. Chimeric antigen receptor T-cell, or CAR T-cell, therapy involves the laboratory reprogramming of a patient’s T cells, which are a type of white blood cell responsible for protecting the body against infection and disease. The T cells are genetically modified to better recognize and attack cancer. The U.S. Food and Drug Administration has approved the immunotherapy procedure for non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia. It is...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
AbstractPurpose of ReviewIMiDs are a class of biologic agents with immunomodulatory, anti-angiogenic, and direct anti-cancer activities. This review summarizes current data on clinical development and application of IMiDs in non-Hodgkin lymphoma (NHL) subtypes, focusing primarily on lenalidomide, with additional discussion on managing common side effects.Recent FindingsImproved upon the prototype thalidomide, the second-generation compound lenalidomide has enhanced immunological and anti-cancer properties with fewer side effects, while next-generation small molecule cereblon/E3 ubiquitin ligase modulator CC-122 is in early...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
BackgroundHigh dose chemotherapy and autologous stem cell transplant (ASCT) results in cure for up to 50% of patients with Hodgkin (HL) and aggressive non-Hodgkin lymphoma (NHL) that relapse after initial treatment with chemo-immunotherapy. Despite improvements in supportive care and patient selection, death after ASCT remains a concern due to progressive disease, infection, and other treatment- and non-treatment-related causes. We evaluated causes and predictors of death in patients undergoing ASCT for HL and NHL.MethodsWe conducted a single-institution, retrospective study of all patients with HL and NHL including diffus...
Source: Blood - Category: Hematology Authors: Tags: 731. Clinical Autologous Transplantation: Results: Poster I Source Type: research
Conclusions: AlloSCT can produce durable remissions in a subset of patients with heavily treated, rel/ref PMBCL. Patients with refractory disease at alloSCT had dismal outcomes. Despite the expanding treatment options available for these patients, alloSCT should be considered in the management of patients with rel/ref PMBCL who are sensitive to salvage therapy.Figure 1A PFS and OS After AlloSCT in Patients with Rel/Ref PMBCLFigure 1B PFS in Patients with Sensitive versus Refractory PMBCL at AlloSCTDisclosuresHerrera: Merck, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bristol-Myers Squibb:...
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results: Poster I Source Type: research
Introduction. Recent research in lymphoma has resulted in better outcomes for clinical trial populations. Population studies have suggested that some real-world patients (pts) have not benefited. We hypothesized that one reason for this discrepancy is the difference between trial participants and real-world pts. We aimed to: 1) Compare demographics and baseline clinical characteristics of real-world and clinical trial pts receiving first-line therapy for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL); and 2) Compare demographics and baseline clinical characteristics of real-...
Source: Blood - Category: Hematology Authors: Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Poster II Source Type: research
Background: The treatment of NHL has witnessed a paradigm shift over time, with targeted immunotherapy, stem cell transplant (SCT) among others. Historically, XRT was used quite frequently for the management of NHL but with advent of better systemic therapy, its utilization has changed. Trends and patterns of care for XRT use have never been formally reported.Methods: We identified patients with NHL diagnosis in the National Cancer Database (NCDB) between years 2004 and 2015. Demographic, clinical, facility level, initial treatment and outcome data were collected. The utilization of XRT in diffuse large B-cell (DLBCL) and ...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Poster III Source Type: research
BackgroundPrimary Thyroid Lymphoma (PTL) is a rare malignancy, representing only 1-5% of thyroid malignancies and 2.5-7% of all extra nodal lymphomas. Most cases of PTL are of B-cell origin, and 98% of all PTL is non-Hodgkin's lymphoma. Case series and case reports represent the majority of the available studies on PTL, with a paucity of large retrospective population studies available for this disease. Due to limited studies the optimal treatment of PTL has not yet been established. Using the National Cancer Database (NDCB) we aimed to evaluate patient characteristics, treatment modalities, and overall survival. This is t...
Source: Blood - Category: Hematology Authors: Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Poster II Source Type: research
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