Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity by Benjamin L. Lampson, Siddha.

Slides:

Advertisements

Similar presentations

Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy.

Advertisements

A disease risk index for patients undergoing allogeneic stem cell transplantation by Philippe Armand, Christopher J. Gibson, Corey Cutler, Vincent T. Ho,

A Phase 1 Study of the Selective Phosphatidylinositol 3-Kinase-Delta (PI3Kδ) Inhibitor, Idelalisib (GS- 1101) in Combination with Rituximab and/or Bendamustine.

OUTCOME MEASURES IN PsA: IMMUNOHISTOLOGY Oliver FitzGerald.

Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia by Alessandra Ferrajoli,

Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD by Ana C. Alho, Haesook T.

Idelalisib plus Bendamustine and Rituximab (BR) Is Superior to BR Alone in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of a.

Copyright © 2014 American Medical Association. All rights reserved.

Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact.

High TCL1 levels are a marker of B-cell receptor pathway responsiveness and adverse outcome in chronic lymphocytic leukemia by Marco Herling, Kaushali.

Interleukin-12 Therapy of Cutaneous T-Cell Lymphoma Induces Lesion Regression and Cytotoxic T-Cell Responses by Alain H. Rook, Gary S. Wood, Elisa K. Yoo,

CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation.

How I treat LGL leukemia

A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL by Jennifer A. Woyach,

Regulatory T cells as a biomarker for response to adalimumab in rheumatoid arthritis Dao X. Nguyen, BSc, Alice Cotton, RN, BSc, Laura Attipoe, MBBS, Coziana.

Volume 129, Issue 1, Pages (July 2005)

CD4+CD25+ regulatory T cells inhibit immune-mediated transgene rejection by David-Alexandre Gross, Marylène Leboeuf, Bernard Gjata, Olivier Danos, and.

CD146 (Mel-CAM), an adhesion marker of endothelial cells, is a novel marker of lymphocyte subset activation in normal peripheral blood by Mohamed F. Elshal,

Feasibility of Lenalidomide Therapy for Persistent Chronic Lymphocytic Leukemia after Allogeneic Transplantation Maria R. Khouri, Elias J. Jabbour, Alison.

A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia by John C. Byrd, Guido Marcucci,

Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells by Lucie Heinzerling,

Immune Reconstitution after Double Umbilical Cord Blood Stem Cell Transplantation: Comparison with Unrelated Peripheral Blood Stem Cell Transplantation

Lenalidomide, idelalisib, and rituximab are unacceptably toxic in patients with relapsed/refractory indolent lymphoma by Chan Yoon Cheah, Loretta J. Nastoupil,

Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis by Lisa A. Michaels, Kwaku.

Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation by George E. Georges, Rainer Storb, Jennifer.

Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia by Rossana Maffei, Silvia Martinelli,

Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kδ inhibitors and VIP antagonists by Christopher T.

Significance of circulating T-cell clones in Sézary syndrome

Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation.

Chronic neutropenia mediated by Fas ligand

Managing Adverse Events With New Oral Therapies in CLL

Human NK cells can control CMV infection in the absence of T cells

Combined CD4+ Donor Lymphocyte Infusion and Low-Dose Recombinant IL-2 Expand FOXP3+ Regulatory T Cells following Allogeneic Hematopoietic Stem Cell Transplantation

Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8+ T-cell restoration.

Up-Regulation of α4β7 Integrin on Peripheral T Cell Subsets Correlates with the Development of Acute Intestinal Graft-versus-Host Disease following Allogeneic.

by Philippe Armand, Christopher J. Gibson, Corey Cutler, Vincent T

Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD by Joanne E. Croudace, Charlotte F.

Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal.

Serum IL-31 levels are increased in a subset of patients with mastocytosis and correlate with disease severity in adult patients Karin Hartmann, MD,

Evolution of a chemosensitive core-binding factor AML into an aggressive leukemia with eosinophilic differentiation by Wenbin Xiao, Mariko Yabe, Michael.

Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients Dan Davini, BA, Fouzia Naeem, MD,

Matthew J. Deeths, Bart T. Endrizzi, Michelle L. Irvin, Lynne P

Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin by Romy M. W. Kremers, Stéphane Zuily, Hilde Kelchtermans,

by Silvia Mele, Stephen Devereux, Andrea G

Engraftment of chronic myelomonocytic leukemia cells in immunocompromised mice supports disease dependency on cytokines by Yanyan Zhang, Liang He, Dorothée.

Serum LAMC2 levels in pancreatic adenocarcinoma (PDAC) and other samples from Japan. Serum LAMC2 levels in pancreatic adenocarcinoma (PDAC) and other samples.

by Geling Li, Emily Waite, and Julie Wolfson

An Open-Label Phase II Randomized Trial of Topical Dexamethasone and Tacrolimus Solutions for the Treatment of Oral Chronic Graft-versus-Host Disease

Low-Dose IL-2 Therapy Preferentially Improves Diversity of the Regulatory T Cell Repertoire in Patients with Refractory Chronic Graft-Versus-Host Disease

Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease by Jennifer S. Whangbo, Haesook.

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation by James N. Kochenderfer,

A phase 1 trial evaluating thioridazine in combination with cytarabine in patients with acute myeloid leukemia by Lili Aslostovar, Allison L. Boyd, Mohammed.

A Prognostic Score for Patients with Acute Leukemia or Myelodysplastic Syndromes Undergoing Allogeneic Stem Cell Transplantation Philippe Armand, Haesook.

Clonotypic heterogeneity in cutaneous T-cell lymphoma (mycosis fungoides) revealed by comprehensive whole-exome sequencing by Aishwarya Iyer, Dylan Hennessey,

Figure 2 Peripheral blood lymphocyte subset counts during dimethyl fumarate treatment(A) Lymphocyte subsets were obtained at baseline (n = 21) and at month.

Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia by Benjamin L. Lampson, Haesook T. Kim, Matthew.

Survival based on V gene mutation status and CD38 expression among B-CLL patients who stratify to the Rai intermediate risk category. Survival based on.

Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables by Andrew W. Roberts, Shuo Ma, Thomas J.

Sarah Nikiforow, Haesook T

Combined BRAFi and anti-CTLA4 administration leads to prolonged antitumor immunity in a patient with metastatic melanoma. Combined BRAFi and anti-CTLA4.

Biology and treatment of Richter syndrome

Increase in proliferation and activation of immune cells in peripheral blood after NKTR-214 treatment. Increase in proliferation and activation of immune.

Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency by Maria Pia Cicalese, Francesca.

Intratumoral changes in critical lymphocyte populations and numbers after NKTR-214 treatment. Intratumoral changes in critical lymphocyte populations and.

CIP2A- and SETBP1-mediated PP2A inhibition reveals AKT S473 phosphorylation to be a new biomarker in AML by Claire M. Lucas, Laura J. Scott, Natasha Carmell,

Gene expression signature that predicts early molecular response failure in chronic-phase CML patients on frontline imatinib by Chung H. Kok, David T.

Interleukin-6 levels predict event-free survival in pediatric AML and suggest a mechanism of chemotherapy resistance by Alexandra M. Stevens, Jennifer.

Ibrutinib decreases ofatumumab-mediated complement-dependent cytotoxicity. Ibrutinib decreases ofatumumab-mediated complement-dependent cytotoxicity. A,

A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia by Susan M. O'Brien, Nicole Lamanna, Thomas.

by Christian Grommes, Sarah S. Tang, Julia Wolfe, Thomas J

Presentation transcript:

Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity by Benjamin L. Lampson, Siddha N. Kasar, Tiago R. Matos, Elizabeth A. Morgan, Laura Rassenti, Matthew S. Davids, David C. Fisher, Arnold S. Freedman, Caron A. Jacobson, Philippe Armand, Jeremy S. Abramson, Jon E. Arnason, Thomas J. Kipps, Joshua Fein, Stacey Fernandes, John Hanna, Jerome Ritz, Haesook T. Kim, and Jennifer R. Brown Blood Volume 128(2):195-203 July 14, 2016 ©2016 by American Society of Hematology

Transaminitis is frequent and severe in subjects receiving idelalisib monotherapy. Transaminitis is frequent and severe in subjects receiving idelalisib monotherapy. (A) An index case of idelalisib-related transaminitis. (B) The fraction of subjects experiencing an ALT elevation of the indicated grade at the indicated time. (C) Swim plot of the indicated toxicities of grade ≥2 at the time that they were first experienced by subjects enrolled in the trial. Other toxicities include one subject with grade 3 rash and 1 subject with grade 3 oral ulcers. Benjamin L. Lampson et al. Blood 2016;128:195-203 ©2016 by American Society of Hematology

Clinical factors are associated with the development of early hepatotoxicity. Clinical factors are associated with the development of early hepatotoxicity. (A) Significant difference in age at enrollment between subjects who experienced no toxicity on trial and those who experienced early hepatotoxicity (P = .02, Mann-Whitney U test). (B) Receiver-operating characteristic (ROC) curves for mutated (M) IGHV status, age ≤65 years, or a combination of the two for predicting the occurrence of early hepatotoxicity. Benjamin L. Lampson et al. Blood 2016;128:195-203 ©2016 by American Society of Hematology

Tissue biopsies and response to steroids suggest an immune-mediated cause for hepatotoxicity. Tissue biopsies and response to steroids suggest an immune-mediated cause for hepatotoxicity. (A) Liver biopsy specimens taken from a normal patient, an otherwise healthy patient with CLL, and a subject with persistent transaminitis after discontinuation of idelalisib. Liver biopsy specimens from patients with CLL demonstrate lymphoid aggregates on hematoxylin and eosin staining (composed of CD20+ B cells, data not shown) as well as increased CD3+ T cells scattered throughout the parenchyma that are increased in number and activation (as assessed by perforin staining) in a subject on idelalisib. (B) A duodenal biopsy specimen from a subject with diarrhea on idelalisib reveals an activated (perforin-positive) CD8+ lymphocytic infiltrate, which is not present in a control sample taken from a subject without CLL. (C) Transaminase levels over time for a subject who, after an unsuccessful attempt at idelalisib reintroduction, was successfully reintroduced to the drug while on steroids. Benjamin L. Lampson et al. Blood 2016;128:195-203 ©2016 by American Society of Hematology

Increased inflammatory cytokine levels and decreased regulatory T-cell levels are associated with the development of toxicities while on idelalisib. Increased inflammatory cytokine levels and decreased regulatory T-cell levels are associated with the development of toxicities while on idelalisib. (A) Serum CCL-3 and (B) CCL-4 levels in subjects at various time points on idelalisib therapy. Baseline values indicated in red are subjects who experienced toxicity at day ∼28, and blue represents subjects who did not experience early hepatotoxicity. Open symbols represent levels drawn when subjects have held idelalisib for 3 to 9 days due to toxicity; closed symbols represent samples drawn while subjects remain on idelalisib. (C) Percentage of CD4+ T cells that are FoxP3+CD25hi regulatory T cells in subjects on idelalisib. (D) Percentage of CD4+ T cells that are CD3+CD4+ FoxP3+CD25hi regulatory T cells in subjects on idelalisib, stratified by toxicity. At baseline, values indicated in red are subjects who experienced toxicity at day ∼28, blue symbols are subjects who did not experience toxicity, and purple symbols are subjects who experienced delayed toxicity and thus contributed data points to the no toxicity group at day ∼28 and the toxicity group at day ∼130. Benjamin L. Lampson et al. Blood 2016;128:195-203 ©2016 by American Society of Hematology