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Resistance to Y-90 Ibritumomab Tiuxetan Therapy

  • Koichiro Abe
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 18)

Abstract

Y-90 ibritumomab tiuxetan is the first radioimmunotherapy (RIT) agent for patients with relapsed or refractory low-grade CD20-positive B-cell non-Hodgkin’s lymphoma. Although accumulated data demonstrate its excellent therapeutic efficiency, there are a certain number of patients that experience disease exacerbation during the post-RIT observation periods. Up to now, advanced disease, bulky mass, poor performance status, a history of frequent chemotherapies before RIT, etc. have been proposed as predictive factors for unfavorable prognosis after RIT. In this chapter, we focus on the bulky disease, the downregulation of the CD20 molecule, the NF-𝜅B activation, and the impaired host immune status as factors presumably related to resistance to Y-90 ibritumomab tiuxetan therapy. We also discuss the mechanisms of the resistance and rational therapeutic approaches. We further illustrate the immunological circumstances in tumor-bearing patients and comment on the immune checkpoint blockade therapy.

Keywords

Y-90 ibritumomab tiuxetan Resistance Bulky mass Downregulation of CD20 NF-𝜅B activation Immunoediting Abscopal effect Immunological cell death Immune checkpoint 

Abbreviations

ABC

Activated B-like diffuse large B-cell lymphoma

ADCC

Antibody-dependent cellular cytotoxicity

Ag

Antigen

APC

Antigen-presenting cell

ATP

Adenosine triphosphate

BT

Bulky tumor

CD

Cluster of differentiation

CDC

Complement-dependent cytotoxicity

ODN

Oligodeoxynucleotides

CR

Complete response

CRR

Complete response rate

CRT

Calreticulin

CTLA-4

Cytotoxic T-lymphocyte-associated protein-4

DA-EPOCH-R

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab

DAMP

Damage-associated molecular patterns

DC

Dendritic cell

DLBCL

Diffuse large B-cell lymphoma

EBRT

Extrabeam radiotherapy

EU

European Union

F(ab′)2

Fab prime 2

Fab

Fragment antigen-binding

Fas-L

Fas-ligand

FcγR

Fcγ receptor

FIT

First-line indolent trial

Flt3-L

Fms-like tyrosine kinase 3 ligand

GCB

Germinal center B cell

GMCSF

Granulocyte macrophage colony-stimulating factor

HcAb

Heavy-chain antibody

HMGB1

High-mobility group box 1

ICD

Immunological cell death

IFN

Interferon

IL

Interleukin

IPI

International Prognostic Index

mAb

Monoclonal antibody

MCL

Mantle-cell lymphoma

MDSC

Myeloid-derived suppressor cells

MHC

Major histocompatibility complex

MRD

Minimal residual disease

NF-κB

Nuclear factor-κB

ORR

Overall response rate

PD-1

Programmed cell death-1

PD-L1

Programed cell death ligand 1

PFS

Progression-free survival

P2RX7

Purinergic receptor P2X, ligand gated ion channel, 7

R-CHOP

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

RIT

Radioimmunotherapy

RN

Radionuclide

scFv

Single-chain variable

TCR

T cell receptor

TGF-β

Transforming growth factor beta

TLR

Toll-like receptor

TNFα

Tumor necrosis factor α

Treg

Regulatory T cells

TTP

Time to disease progression

US FDA

US Food and Drug Administration

Y-90

Yttrium-90

Notes

Acknowledgments

We are indebted to Professors M Harada and K Tamada for their helpful discussions about the immunological cell death and the immune checkpoint blockade therapy.

Conflict of Interest

No conflict statement: No potential conflicts of interest were disclosed.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Diagnostic Radiology and Nuclear MedicineTokyo Women’s Medical UniversityTokyoJapan

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