Fast Facts: CAR T-Cell Therapy in Diffuse Large B-Cell Lymphoma

D. Moloney, R.J. Buka

Description

Diffuse large B-cell lymphoma (DLBCL) is the most common form of high-grade non-Hodgkin lymphoma. While treatment with immunochemotherapy has generally shown good outcomes, specific subgroups of patients with high-risk disease have an unfavorable prognosis. Extensive efforts have been made to improve outcomes in these patients. As such, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become the new standard of care for patients with relapsed or refractory DLBCL after at least two prior lines of therapy. It is an exciting new therapeutic intervention that is integral to the concept of personalized medicine. Table of Contents: • DLBCL: an overview • CAR T cells • CAR T-cell products • Delivering CAR T-cell therapy and managing patient expectations • CAR T-cell therapy-related toxicities

Sujets

• Hermatology
• Medical
• Médecine

Informations

• Publié par: S. Karger AG
• Date de parution: 30 septembre 2021
• Nombre de lectures: 0
• EAN13: 9783318069358
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Fast Facts: CAR T-Cell Therapy in Diffuse Large B-Cell Lymphoma
First published 2021
Text 2020 Richard J Buka, Deirdre Moloney
2021 in this edition S. Karger Publishers Ltd
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eISBN 978-3-318-07024-8
Buka RJ (Richard)
Fast Facts: CAR T-Cell Therapy in Diffuse Large B-Cell Lymphoma/Richard J Buka, Deirdre Moloney
Medical illustrations by Graeme Chambers, Belfast, UK.
Typesetting by Amnet, Chennai, India.
Printed in the UK with Xpedient Print.
Contents
List of abbreviations
Introduction
DLBCL: an overview
CAR T cells
CAR T-cell products
Delivering CAR T-cell therapy and managing patient expectations
CAR T-cell therapy-related toxicities
Useful resources
Index
List of abbreviations
ABC: activated B-cell-like (subtype)
ALT: alanine aminotransferase
AST: aspartate aminotransferase
ASTCT: American Society for Transplantation and Cellular Therapy
B-ALL: B-cell acute lymphoblastic leukemia
BCR: B-cell receptor
CAPD: Cornell Assessment of Pediatric Delirium
CAR: chimeric antigen receptor
CD: cluster of differentiation
CIBMTR: Center for International Blood and Marrow Transplant Research
CR: complete response
CRP: C-reactive protein
CRS: cytokine release syndrome
CT: computed tomography
DLBCL: diffuse large B-cell lymphoma
DMSO: dimethyl sulfoxide
DNA: deoxyribonucleic acid
EBMT: European Society for Blood and Marrow Transplantation
EMA: European Medicines Agency
Fab: fragment antigen-binding (region)
Fc: fragment crystallizable (region)
FDA: Food and Drug Administration
Fv: fragment variable (region)
GCB: germinal center B-cell-like (subtype)
G-CSF: granulocyte colony-stimulating factor
GEP: gene expression profiling
GvHD: graft-versus-host disease
HIV: human immunodeficiency virus
HLH/MAS: hemophagocytic lymphohistocytosis/macrophage activation syndrome
HSCT: hematopoietic stem cell transplantation
ICANS: immune effector cell-associated neurotoxicity syndrome
ICE: Immune Effector Cell-associated Encephalopathy (score)
IFN: interferon
Ig: immunoglobulin
IL: interleukin
MHC: major histocompatibility complex
MRI: magnetic resonance imaging
NCCN-IPI: National Comprehensive Cancer Network International Prognostic Index
NHL: non-Hodgkin lymphoma
NOS: (DLBCL) not otherwise specified
OS: overall survival
PFS: progression-free survival
PR: partial response
RCT: randomized controlled trial
R-IPI: revised International Prognostic Index
RNA: ribonucleic acid
TCR: T-cell receptor
TLS: tumor lysis syndrome
WHO: World Health Organization
Chemotherapy regimens
MATRix-RICE: (MATRix) methotrexate, Ara-C (cytarabine), thiotepa and rituximab; (RICE) rituximab plus ifosfamide, carboplatin and etoposide
Pola-BR: polatuzumab-vedotin, bendamustine and rituximab
R-ACVBP: rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone
R-CHOEP: rituximab plus cyclophosphamide, doxorubicin, vincristine, etoposide and prednisolone
R-CHOP: rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone
R-CODOX-M: rituximab plus cyclophosphamide, vincristine, doxorubicin and methotrexate
[R-]DHAP: [rituximab plus] dexamethasone, high-dose Ara-C (cytarabine) and platinum (cisplatin)
[R-]ESHAP: [rituximab plus] etoposide, steroid (methylprednisolone), high-dose Ara-C (cytarabine) and platinum (cisplatin)
R-IVAC: rituximab plus ifosfamide, etoposide and Ara-C (cytarabine)
Introduction
Diffuse large B-cell lymphoma (DLBCL) is the most common form of high-grade non-Hodgkin lymphoma. While treatment with immunochemotherapy has generally shown good outcomes, specific subgroups of patients with high-risk disease have an unfavorable prognosis. Extensive efforts have been made to improve outcomes in these patients. As such, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become the new standard of care for patients with relapsed or refractory DLBCL after at least two prior lines of therapy. It is an exciting new therapeutic intervention that is integral to the concept of personalized medicine.
Here, as well as providing an overview of how CAR T cells work, current and emerging products and the results of clinical trials, we look at the key role of nurses in the education of, and communication with, patients and caregivers and the multidisciplinary delivery and coordination of CAR T-cell therapy. Clear and accurate patient education and good communication and coordination between the treatment center and the referring center, leading up to and following CAR T-cell therapy, is essential for successful outcomes in eligible patients.
In particular, we look at the nurse s role in managing the frequent short-term toxicities associated with CAR T-cell therapy and longer-term monitoring, as well as how to manage patients treatment expectations. We hope this will be a valuable resource for all nurses caring for patients and the needs of their family members, as well as other members of the multidisciplinary team.
1
DLBCL: an overview
Hematopoiesis is the highly controlled process by which blood cells are made and mature. It can go wrong at any point, by virtue of numerous genetic faults, resulting in distinctly different diseases. Lymphomas are cancers that originate from lymphoid cells - T lymphocytes (T cells), B lymphocytes (B cells), natural killer cells - and their progenitors ( Figure 1.1 ). As the name suggests, diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells.
Epidemiology and classification
Simplistically, lymphomas can be categorized as Hodgkin lymphoma and non-Hodgkin lymphoma (NHL), with the latter further subcategorized as high-grade (aggressive disease) or low-grade (slow-growing, indolent disease) NHL. Through the course of the disease, low-grade lymphoma can transform into high-grade lymphoma. This is important for CAR T-cell approvals, which are discussed later. NHL makes up around 4% of all cancer cases in both the UK and USA. 1 , 2 DLBCL not otherwise specified (NOS) is the most common high-grade lymphoma, comprising 30-40% of all NHL. 3 , 4 It is an aggressive cancer with a median age of onset of about 70 years and has a slight male predominance.

Figure 1.1 Development of lymphoid cells from hematopoietic stem cells (HSC) to terminally differentiated cells through intermediate progenitors.
Subclassification. Gene expression profiling (GEP) can be used to subclassify DLBCL NOS into two principal molecular subtypes. 5
The germinal center B-cell-like (GCB) subtype is derived from B cells in the germinal center of secondary lymphoid organs.
The activated B-cell-like (ABC) subtype is derived from a more mature stage in the B-cell life cycle after it has traversed the germinal center.
Defining these two DLBCL subtypes has prognostic relevance, as GCB-DLBCL has a significantly better prognosis than ABC-DLBCL. 6 , 7 As GEP is not in mainstream clinical use, analysis of immunohistochemical staining patterns can be used to assign the subtype. 8
Finally, there are a number of lymphomas that are closely related to DLBCL, including primary mediastinal B-cell lymphoma, primary CNS lymphoma and testicular lymphoma. The distinctions are beyond the scope of this book but are important, as they may require specific treatments and may or may not be eligible for CAR T-cell therapy.
Diagnosis
Clinical presentation. DLBCL may present with enlarged lymph nodes and/or symptoms that include fever, weight loss or night sweats, otherwise known as B symptoms . 9
Many conditions can mimic lymphoma, including infectious diseases such as Epstein-Barr virus (EBV), tuberculosis and syphilis, autoimmune diseases such as sarcoidosis, and benign self-limiting conditions such as Kikuchi lymphadenitis.
Although DLBCL is often confined to the lymph nodes ( nodal disease), as lymphocytes reside in other tissues it can also involve extranodal sites, including the gastrointestinal tract, lungs, skin, kidneys, adrenal glands, brain, bones and other soft tissues, and can thus present in many different ways.
Work-up should include a detailed history and examination, extensive blood