Resistance to Ibritumomab in Lymphoma (Resistance to Targeted Anti-Cancer Therapeutics, 18)

This volume, in discussing resistance to ibritumomab, will focus on the mechanism, hematological aspects, radiological and nuclear medicine aspects, and medical physics that deal with radiation dosimetry, and will outline future prospects for overcoming resistance and enhancing efficacy of ibritumomab. “Resistance to Targeted Anti-Cancer Therapeutics”: Aims and Scope 5 Preface 7 Biography of Series Editor 6 Acknowledgments 9 Contents 10 Clinical Use and Efficacy of Ibritumomab in B Cell Lymphoma 11 1 Introduction 12 2 Characteristics of Zevalin 12 3 Treatment Schedule and Dosage of Zevalin 12 4 Patient Eligibility 13 5 Zevalin in Relapse or Refractory Patients 13 6 Zevalin in Frontline Therapy 13 7 Toxicities and Safety Profile 14 8 Factor Associated with Effects of Zevalin 15 9 Future Aspects 15 References 15 Biology and Pathology of B-Cell Lymphoma 19 1 Introduction 20 2 Cellular Origin of B-Cell Lymphomas 22 3 Transforming Events 28 4 Viruses in B-Cell Lymphomas 33 5 Microenvironmental Interactions in B-Cell Lymphomas and the Role of the BCR 34 6 Conclusion 36 References 37 Resistance to Y-90 Ibritumomab Tiuxetan Therapy 42 1 Introduction 44 2 Bulky Disease 45 3 Downregulation of CD20 47 4 NF-κB Activation 50 5 Impaired Host Immune Status 51 5.1 Immunoediting 51 6 Effect of Ionizing Radiation on the Immune Systems 53 7 Combination of RT and Immune Checkpoint Blockade Therapy 55 8 Conclusion 56 References 57 Features of Ibritumomab as Radionuclide Therapy 67 1 Introduction 68 2 Radioimmunotherapy with Ibritumomab 68 3 Features of Ibritumomab 70 4 A Model of Theranostic Approach 71 5 Enhancing Efficacy of Ibritumomab Tiuxetan 72 6 Conclusion 72 References 73 Radiological Evaluation of Response and Resistance of Ibritumomab 75 1 Introduction 76 2 Evaluation of FDG-PET/CT for Monitoring the Response to RIT 76 2.1 FDG-PET/CT Imaging 79 3 Summary of the Results 80 4 Discussion 82 5 Conclusions 84 References 84 Characteristics of Ibritumomab as Radionuclide Therapy Agent 86 1 Introduction 87 2 CD 20: B-Cell Antigen 88 3 mAb Targeting CD20 89 4 Ibritumomab Tiuxetan Coupled with Radioisotopes 90 4.1 Ibritumomab 90 4.2 Tiuxetan 91 4.3 Radionuclides 91 5 Yttrium-90 (90Y) 93 6 Indium-111 (111In) 93 7 Preclinical Investigation of 90Y-/111In-Ibritumomab Tiuxetan 94 7.1 In Vitro Studies 94 7.2 Ex Vivo/In Vivo Studies 95 8 Imaging and Therapy Protocol 96 8.1 Preparation of 90Y-Ibritumomab Tiuxetan 96 8.2 Schedule of 90Y-Ibritumomab Tiuxetan Therapy 96 9 Perspectives and Conclusion 98 References 99 Resistance and Heterogeneity of Intratumoral Antibody Distribution 105 1 Introduction 105 2 SPECT/CT and PET/CT System 106 3 Statistical Approach Taken to Characterize Lesion’s Uptake 107 4 Resistance and Heterogeneity of Intratumoral Antibody Distribution 107 5 Conclusions and Perspectives 108 References 108 Radiation Dosimetry in Ibritumomab Therapy 111 1 Introduction 112 2 Activity Escalation Trial and Dose Escalation Trial 112 3 Dosimetry for Molecular Radiotherapy 113 3.1 Quantification of Pharmacokinetics 114 3.2 Kinetic Model 114 3.3 Prediction of Pharmacokinetics During Therapy 115 3.4 Absorbed Dose Calculations 115 3.5 Treatment Planning 116 3.6 Treatment and Quality Control Measurements 116 3.7 Conclusion 117 4 Dosimetry for Ibritumomab Tiuxetan 117 5 Treatment Planning for [90Y]Ibritumomab Tiuxetan 119 6 Conclusion and Outlook 119 References 120 Combining RAIT and Immune-Based Therapies to Overcome Resistance in Cancer? 124 1 Introduction 126 2 Ionizing Radiation and Antitumor Immunity 126 2.1 Abscopal Effect: An Aftermath of Ionizing Radiation Involving the Immune System 126 2.2 Immunological Effects of Ionizing Radiation 127 2.3 Modulation of Tumor Cell Immunogenicity 128 2.4 Immunogenic Cell Death 129 2.5 Secretion of Cytokines 130 2.6 Blood Vessels 130 3 Combining Ionizing Radiation and Immunotherapy 130 3.1 Preclinical Evidence in Hematopoietic Cancer Models 130 3.1.1 Radiotherapy and Immunotherapy 130 3.1.2 Radioimmunotherapy and Immunotherapy 133 3.2 Clinical Evidence 134 3.2.1 Radiotherapy and Immunotherapy 134 3.2.2 Radioimmunotherapy and Immunotherapy 135 4 Conclusions and Perspectives 136 References 137 Prospects for Enhancing Efficacy of Radioimmunotherapy 143 1 Introduction 144 2 Current Limitations of RIT 145 3 Prospects to Improve RIT 145 3.1 Fractionation of Injections 145 3.2 Combinations with Other Therapeutic Agents 147 3.3 Pretargeting Using Bispecific Antibodies 149 3.4 Alpha-Emitting Radionuclides 150 3.5 Theranostic Approaches: Imaging of Radiolabeled Antibodies to Improve RIT Procedures 153 4 Conclusion 154 References 155 Index 158 Front Matter ....Pages i-xiii Clinical Use and Efficacy of Ibritumomab in B Cell Lymphoma (Ilseung Choi, Naokuni Uike)....Pages 1-8 Biology and Pathology of B-Cell Lymphoma (Yoichi Tatsumi)....Pages 9-31 Resistance to Y-90 Ibritumomab Tiuxetan Therapy (Koichiro Abe)....Pages 33-57 Features of Ibritumomab as Radionuclide Therapy (Makoto Hosono)....Pages 59-66 Radiological Evaluation of Response and Resistance of Ibritumomab (Takayoshi Ishimori, Koya Nakatani)....Pages 67-77 Characteristics of Ibritumomab as Radionuclide Therapy Agent (Hidekazu Kawashima)....Pages 79-97 Resistance and Heterogeneity of Intratumoral Antibody Distribution (Kohei Hanaoka, Makoto Hosono)....Pages 99-104 Radiation Dosimetry in Ibritumomab Therapy (Gerhard Glatting)....Pages 105-117 Combining RAIT and Immune-Based Therapies to Overcome Resistance in Cancer? (Jean-Baptiste Gorin, Jérémie Ménager, Yannick Guilloux, Jean-François Chatal, Joëlle Gaschet, Michel Chérel)....Pages 119-137 Prospects for Enhancing Efficacy of Radioimmunotherapy (Clément Bailly, Caroline Bodet-Milin, François Guérard, Caroline Rousseau, Michel Chérel, Françoise Kraeber-Bodéré et al.)....Pages 139-153 Back Matter ....Pages 155-158