by Jennifer N. Brudno, and James N. Kochenderfer

Slides:

Advertisements

Similar presentations

Safe and Effective Re-Induction of Complete Remissions in Adults with Relapsed B-ALL Using 19-28z CAR CD19-Targeted T Cell Therapy Davila ML et al. Proc.

Advertisements

Kochenderfer JN et al. Proc ASH 2013;Abstract 168.

Lee DW III et al. Proc ASH 2013;Abstract 68.

T Cells Engineered with a Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Produce Significant in Vivo Proliferation, Complete Responses and Long-Term.

Maude et al. BLOOD, 25 JUNE 2015 x VOLUME 125, NUMBER 26

1 Presented by Martin Cohen, M.D. at the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee.

The Role of Immunotherapy for the Treatment of Hematologic Malignancies Patrick Stiff MD Coleman Professor of Oncology Loyola University Medical Center.

Table 1. Blood oxygenation, heart function, myocardial enzyme spectrum, and blood cell count data before and after the fetal death delivery in a 28 year.

chimeric antigen receptor T-cell therapy for ALL

Professor John Gribben Barts Cancer Institute

Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation by Surbhi Shah, Faye L. Norby, Yvonne.

GVHD-associated immunodeficiency: soil or seed?

Adoptive Immunotherapy Following Umbilical Cord Blood Transplantation Using The Sleeping Beauty System and Artificial Antigen Presenting Cells To Generate.

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate-

Immunotherapy for lymphoma: The time is now

Nonengraftment Haploidentical Cellular Immunotherapy for Refractory Malignancies: Tumor Responses without Chimerism Gerald A. Colvin, David Berz, Muthalagu.

Bulging glands? Blame it on B cells

Gupta V, Tallman MS, Weisdorf DJ

When monocyte life hangs by a thread

A Clinical Evaluation of the International Lymphoma Study Group Classification of Non-Hodgkin's Lymphoma Blood Volume 89(11): June 1, 1997 ©1997.

Evidence for increased risk of secondary graft failure after in vivo depletion of suicide gene-modified T lymphocytes transplanted in conjunction with.

Successful Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant in an Acute Leukemia Patient With Chemotherapy-Induced Marrow Aplasia and Progressive.

BRAF inhibitor: targeted therapy in hairy cell leukemia

Research Techniques Made Simple: CAR T-Cell Therapy

Figure 1 Chimeric antigen receptor (CAR) structures

Antibody-modified T cells: CARs take the front seat for hematologic malignancies by Marcela V. Maus, Stephan A. Grupp, David L. Porter, and Carl H. June.

T regulatory cells turn on T regulatory cells

Gnawing at Metchnikoff’s paradigm

by Corey S. Cutler, John Koreth, and Jerome Ritz

Functional neutrophils from human ES cells

Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer by Jeffrey S. Miller, Yvette Soignier, Angela.

Transient proliferation of donor-derived ATL cell–like lymphocytes early after allogeneic stem cell transplantation in an adult T-cell leukemia/lymphoma.

Has the T cell bitten off more than it can chew?

by Jayesh Mehta Blood Volume 112(2): July 15, 2008

Rare cells predict GVHD

Figure 1 Clinical case study

Volume 25, Issue 10, Pages (October 2017)

Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia Robert Iannone, James F Casella, Ephraim.

Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific antitumor immunity from T-cell populations undergoing.

Targeted Therapeutics

Volume 25, Issue 3, Pages (March 2017)

Clinical Utility of Quantitative PCR for Chimerism and Engraftment Monitoring after Allogeneic Stem Cell Transplantation for Hematologic Malignancies

Yu-Waye Chu, Ronald E. Gress

Leukemia Lineage-Specific Chimerism Analysis and Molecular Monitoring Improve Outcome of Donor Lymphocyte Infusions Darius Sairafi, Mats Remberger, Michael.

Research Techniques Made Simple: CAR T-Cell Therapy

Allogeneic Transplantation for Pediatric Acute Lymphoblastic Leukemia: The Emerging Role of Peritransplantation Minimal Residual Disease/Chimerism Monitoring.

Normal Immunologic Response to a Neoantigen, Bacteriophage ΦX-174, in Baboons With Long-Term Lymphohematopoietic Reconstitution From Highly Purified CD34+

Evaluation of Initial Telomere Length and Changes after Transplantation in Adult Double-Unit Cord Blood Transplant Recipients Beth Ashbridge, Ahmet Zehir,

Volume 21, Issue 4, Pages (April 2013)

Volume 23, Issue 1, Pages (January 2015)

Nat. Rev. Clin. Oncol. doi: /nrclinonc

by Shannon L. Maude, David T. Teachey, David L. Porter, and Stephan A

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

Management of Cytokine Release Syndrome (CRS) in Patients Undergoing Chimeric Antigen Receptor Modified (CAR) T-Cell Therapy Following Autologous Stem.

Chimeric Antigen Receptor–Modified T Cells: Clinical Translation in Stem Cell Transplantation and Beyond Stanley R. Riddell, Michael C. Jensen, Carl.

by Christine L. Kempton, and Amanda B. Payne

Volume 21, Issue 11, Pages (November 2013)

Molecular Therapy Volume 21, Pages S247-S248 (May 2013)

Engineering of Chimeric Antigen Receptor therapy.

What’s your nationality? Where are you from?

Proposed model of molecular pathogenesis in the development and progression of major subtypes of MCL. Precursor B cells usually with but sometimes without.

High Response Rate to Donor Lymphocyte Infusion after Allogeneic Stem Cell Transplantation for Indolent Non-Hodgkin Lymphoma Adrian J.C. Bloor, Kirsty.

Bigger, Stronger, Faster: Chimeric Antigen Receptor T Cells Are Olympic Killers by Paul J Neeson, Alexander James Davenport, Joseph A Trapani, Michael.

by Daniel W. Lee, Rebecca Gardner, David L. Porter, Chrystal U

How I vaccinate blood and marrow transplant recipients

Optimal Donor Selection: Beyond HLA

by Lapo Alinari, and Kristie A. Blum

Chimeric antigen receptor–modified T cells: CD19 and the road beyond

Normal pathway of B12 absorption and cellular uptake.

CD123 CAR T cells for the treatment of myelodysplastic syndrome

Presentation transcript:

by Jennifer N. Brudno, and James N. Kochenderfer Toxicities of chimeric antigen receptor T cells: recognition and management by Jennifer N. Brudno, and James N. Kochenderfer Blood Volume 127(26):3321-3330 June 30, 2016 ©2016 by American Society of Hematology

CRS toxicities by organ system. CRS toxicities by organ system. After infusion of CAR T cells, CRS toxicities affecting a wide variety of organs can occur. Professional illustration by Patrick Lane, ScEYEnce Studios. Jennifer N. Brudno, and James N. Kochenderfer Blood 2016;127:3321-3330 ©2016 by American Society of Hematology

Response to tocilizumab in 2 patients. Response to tocilizumab in 2 patients. Patient 1 is a 54-year-old male who received T cells transduced with a CAR targeting B-cell maturation antigen. He experienced CRS starting 4 hours following T-cell infusion, with development of fevers, tachycardia, tachypnea, hypoxia, and hypotension requiring vasopressors. (A) Patient 1 received tocilizumab 25 hours after his cell infusion, which was followed by a transient decrease in temperature and heart rate. He experienced worsening CRS and received a second dose of tocilizumab on day 5 following cell infusion, which was followed by a sustained decrease in temperature and heart rate. (B) The respiratory rate of patient 1 decreased following his first dose of tocilizumab, and intubation was avoided. (C) Patient 2 is a 20-year-old woman with a history of ALL with a past history of a matched-related donor SCT. She received donor-derived T cells transduced with a CAR targeting CD19 for progressive ALL after transplant. She experienced CRS toxicity with fevers, tachycardia, tachypnea, hypoxia, left ventricular systolic dysfunction, prolonged activated PTT, and increased creatine kinase. She received tocilizumab on day 4 following CAR T-cell infusion. Her respiratory rate decreased following tocilizumab, and intubation was avoided. (D) The heart rate of patient 2 decreased following tocilizumab. (E) Following tocilizumab, CRP in patient 2 decreased over a period of days. Professional illustration by Patrick Lane, ScEYEnce Studios. Jennifer N. Brudno, and James N. Kochenderfer Blood 2016;127:3321-3330 ©2016 by American Society of Hematology

General treatment algorithm for CRS and neurologic toxicities. General treatment algorithm for CRS and neurologic toxicities. A general algorithm used for treatment of CAR T-cell toxicity occurring in patients at the NCI Experimental Transplantation and Immunology Branch is shown. Professional illustration by Patrick Lane, ScEYEnce Studios. Jennifer N. Brudno, and James N. Kochenderfer Blood 2016;127:3321-3330 ©2016 by American Society of Hematology