Management of autoimmune complications in patients with lymphoid cancer

Blood ◽

10.1182/blood.2019003686 ◽

2021 ◽

Author(s):

Edit Anna Porpaczy ◽

Ulrich Jaeger

Keyword(s):

Checkpoint Inhibitors ◽

Cell Receptor ◽

Malignant Lymphomas ◽

Autoimmune Conditions ◽

Autoimmune Cytopenias ◽

Anti Cd20 ◽

Chronic Lymphoproliferative Diseases ◽

Work Up ◽

Indication For Treatment ◽

Lymphoma Therapy

Autoimmune conditions can occur at any temporary relationship with malignant lymphomas. In many instances, treatment at diagnosis is not required, but symptomatic autoimmune conditions represent an indication for treatment particularly in chronic lymphoproliferative diseases. Treatment is selected depending on the predominant condition - autoimmune disease (immunosuppression) or lymphoma (anti-lymphoma therapy). Steroids as well as anti-CD20 antibodies are effective against both and may suppress the autoimmune complication for a prolonged period. Efficacy of B-cell receptor inhibitors has provided us with novel insights into the pathophysiology of antibody-producing B-cells. Screening for underlying autoimmune conditions is part of the lymphoma work-up since other drugs like immunomodulators or checkpoint inhibitors should be avoided or used with caution. Here we discuss diagnostic challenges and treatment approaches for different situations involving lymphomas and autoimmune cytopenias.

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Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

Thai Journal of Hepatology ◽

10.30856/th.jhep2018vol1iss1_07 ◽

2018 ◽

Vol 1 (1) ◽

pp. 28-32

Author(s):

Piyawat Komolmit

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Major Histocompatibility Complex ◽

T Cell Receptor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cell Receptor ◽

Immune Checkpoints ◽

Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

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CNS demyelination associated with immune dysregulation and a novel CTLA-4 variant

Multiple Sclerosis Journal ◽

10.1177/1352458520963896 ◽

2021 ◽

pp. 135245852096389

Author(s):

Stefania Kaninia ◽

Alexandros Grammatikos ◽

Kathryn Urankar ◽

Shelley A Renowden ◽

Nikunj K Patel ◽

...

Keyword(s):

T Cell Activation ◽

Cell Activation ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Novel Treatments ◽

First Case ◽

Self Tolerance ◽

Autoimmune Conditions ◽

History Of ◽

Cns Demyelination

Background: The cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway acts as a negative immune regulator of T-cell activation and promotes self-tolerance. Case: We report the first case of biopsy-proven central nervous system inflammatory demyelination in the context of primary immunodeficiency and a novel CTLA-4 variant. Conclusion: This case has significant implications for the development of novel treatments for autoimmune conditions including multiple sclerosis and further emphasises the need for caution with clinical use of CTLA-4 immune checkpoint inhibitors in those with a history of inflammatory demyelination.

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COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001870 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001870

Author(s):

Angelo Dipasquale ◽

Pasquale Persico ◽

Elena Lorenzi ◽

Daoud Rahal ◽

Armando Santoro ◽

...

Keyword(s):

Lung Injury ◽

Head And Neck ◽

Checkpoint Inhibitors ◽

Experimental Therapy ◽

Common Mechanism ◽

Nasopharyngeal Swab ◽

Immune Mediated ◽

Diagnostic Work ◽

Work Up ◽

Diagnostic Work Up

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65–year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.

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NOVEL DRUGS IN FOLLICULAR LYMPHOMA

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2016.061 ◽

2016 ◽

Vol 8 ◽

pp. 2016061 ◽

Cited By ~ 5

Author(s):

Giuseppe Rossi ◽

Antonella Anastasia

Keyword(s):

Follicular Lymphoma ◽

Treatment Strategies ◽

Cell Receptor ◽

Phase Iii ◽

Non Hodgkin Lymphoma ◽

Free Treatment ◽

Phase Iii Trials ◽

New Treatment ◽

Anti Cd20 ◽

Key Steps

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of a chieving a definite cure, have prompted investigations into the possible role of more effective and less toxic strategies with innovative therapeutic agents. Recently Casulo et al demonstrated that approximately 20% of patients with FL actually relapse within 2 years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis.Evolving strategies for difficult to treat FL patients have recently considered immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), with mAbs directed against other surface antigens such as CD22 and CD23 (epratuzumab, lumiliximab), with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inibithors(idelalisib, duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies, taking into account their toxicity. Of course we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

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Whole-Body Imaging to Assess Cell-Based Immunotherapy: Preclinical Studies with an Update on Clinical Translation

Molecular Imaging and Biology ◽

10.1007/s11307-021-01669-y ◽

2021 ◽

Author(s):

Noriko Sato ◽

Peter L. Choyke

Keyword(s):

T Cell ◽

Cell Tracking ◽

Checkpoint Inhibitors ◽

Cell Receptor ◽

Clinical Translation ◽

Whole Body ◽

Whole Body Imaging ◽

Body Imaging ◽

Cell Therapies

AbstractIn the past decades, immunotherapies against cancers made impressive progress. Immunotherapy includes a broad range of interventions that can be separated into two major groups: cell-based immunotherapies, such as adoptive T cell therapies and stem cell therapies, and immunomodulatory molecular therapies such as checkpoint inhibitors and cytokine therapies. Genetic engineering techniques that transduce T cells with a cancer-antigen-specific T cell receptor or chimeric antigen receptor have expanded to other cell types, and further modulation of the cells to enhance cancer targeting properties has been explored. Because cell-based immunotherapies rely on cells migrating to target organs or tissues, there is a growing interest in imaging technologies that non-invasively monitor transferred cells in vivo. Here, we review whole-body imaging methods to assess cell-based immunotherapy using a variety of examples. Following a review of preclinically used cell tracking technologies, we consider the status of their clinical translation.

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A Rare Case of Rituximab Induced Allergic Interstitial Nephritis with a Good Response to Glucocorticoids

10.33169/biomcase.bacroaoj-2-122 ◽

2021 ◽

Vol 2 (2) ◽

pp. 80-83

Author(s):

Vrushali Dabak

Keyword(s):

Interstitial Nephritis ◽

Kidney Biopsy ◽

Central Nervous System Lymphoma ◽

Hematologic Malignancies ◽

Drug Induced ◽

First Case ◽

Autoimmune Conditions ◽

Anti Cd20 ◽

High Index Of Suspicion ◽

Wide Usage

Rituximab is a chimeric anti-CD20 monoclonal antibody that has been widely used to treat CD 20 positive hematologic malignancies and some autoimmune conditions. Although usually well tolerated, an increasing number of serious complications related to rituximab have been noted with its wide usage. We report a 67-year-old man who developed biopsy-proven Allergic Interstitial Nephritis (AIN) after treatment with rituximab for his Primary Central Nervous System Lymphoma (PCNSL). Rituximab-induced AIN was confirmed by kidney biopsy, and his kidney function improved to his baseline with supportive care and four weeks of steroid treatment. While rare, AIN could be a possible adverse effect of rituximab. To our knowledge, this is the first case report of a biopsy-proven AIN from rituximab. The association of AIN and rituximab in our case necessitates a high index of suspicion to facilitate early detection of AIN and timely discontinuation of the offending medication. Keywords: Rituximab; Drug induced allergic interstitial nephritis.

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Pre-existing and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs

Blood ◽

10.1182/blood.2020008201 ◽

2021 ◽

Author(s):

Candida Vitale ◽

Chiara Salvetti ◽

Valentina Griggio ◽

Marika Porrazzo ◽

Luana Schiattone ◽

...

Keyword(s):

Monoclonal Antibody ◽

Immunosuppressive Agents ◽

Lymphocytic Leukemia ◽

Targeted Drugs ◽

Treatment Groups ◽

Beneficial Impact ◽

History Of ◽

Targeted Drug ◽

Autoimmune Cytopenias ◽

Anti Cd20

Autoimmune cytopenias (AIC) affect 5-9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs - ibrutinib, idelalisib and venetoclax - have a prominent role in the treatment of CLL, but their impact on CLL-associated AIC is largely unknown. In this study, we evaluated the characteristics and outcome of pre-existing AIC, and described the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of pre-existing AIC was reported in 104/815 patients (13%). Interestingly, 80% of patients whose AIC was not resolved at the time of targeted drug start experienced an improvement or a resolution during therapy. Treatment-emergent AIC occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib and in 7% during venetoclax, with an estimated incidence rate of 5, 6 and 69 episodes per 1000 patients per year of exposure in the three treatment groups, respectively. The vast majority of patients who developed treatment-emergent AIC carried unfavorable biological features such as an unmutated IGHV, and a del(17p) and/or TP53 mutation. Notably, despite AIC, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib and venetoclax appears to have a beneficial impact on CLL-associated AIC, inducing an improvement or even a resolution of pre-existing AIC in most cases and eliciting treatment-emergent AIC in a negligible portion of patients.

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Pharmacokinetics and Systems Pharmacology of Anti-CD47 Macrophage Immune Checkpoint Inhibitor Hu5F9-G4

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117666190820105134 ◽

2020 ◽

Vol 17 (1) ◽

pp. 14-24 ◽

Cited By ~ 1

Author(s):

Adarsh Mishra ◽

Ishant Kataria ◽

Sujit Nair

Keyword(s):

Annual Meeting ◽

Immune Checkpoint ◽

Cancer Care ◽

Checkpoint Inhibitors ◽

B Cell Lymphoma ◽

Great Promise ◽

Systems Pharmacology ◽

Immunoglobulin G4 ◽

American Society ◽

Anti Cd20

Background: Hu5F9-G4, a human immunoglobulin G4 (IgG4) monoclonal antibody (mAb) has recently been granted fast-track designation by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Hu5F9-G4 has the ability to block CD47-SIRPα signaling along with anti- EGFR and anti-PD-L1 immune checkpoint activity that is involved in a variety of cancers like solid tumors, Non-Hodgkin’s Lymphoma (NHL), colorectal cancer (CRC), breast, ovarian and bladder cancers, and hematological malignancies. Thus, Hu5F9-G4 is an important biologic that has increasing clinical relevance in cancer care. Methods: We queried PubMed, Web of Science, Google Scholar, Science Direct and Scopus databases with keywords pertaining to Hu5F9-G4. In addition, we have included the Hu5F9-G4 data presented at the 60th American Society of Hematology (ASH) Annual Meeting, the American Society of Clinical Oncology (ASCO) Annual Meeting and 23rd Congress of the European Hematology Association (EHA). Results: We discuss the mechanistic basis and preclinical evidence for the anticancer activity of Hu5F9-G4. Further, we delineate clinical studies, alone and in combination with anti-CD20 mAb rituximab, anti-EGFR mAb cetuximab, PD-L1 checkpoint inhibitors avelumab and atezolizumab, and anti-HER2 mAb trastuzumab. Moreover, the potential adverse effects, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 with emphasis on the role of CD47-SIRPα signaling in phagocytosis are presented. Conclusions: Taken together, we review the pharmacokinetics and systems pharmacology of Hu5F9-G4 which appears to hold great promise for the future of cancer care.

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From Tumor Mutational Burden to Blood T Cell Receptor: Looking for the Best Predictive Biomarker in Lung Cancer Treated with Immunotherapy

Cancers ◽

10.3390/cancers12102974 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2974

Author(s):

Andrea Sesma ◽

Julián Pardo ◽

Mara Cruellas ◽

Eva M. Gálvez ◽

Marta Gascón ◽

...

Keyword(s):

Lung Cancer ◽

T Cell ◽

T Cell Receptor ◽

Checkpoint Inhibitors ◽

Predictive Biomarker ◽

Cell Receptor ◽

Mutational Burden ◽

Tcr Repertoire ◽

Tumor Mutational Burden ◽

Tumor Immunogenicity

Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain low in unselected patients and a large proportion of patients undergo disease progression in the first weeks of treatment. Therefore, there is a need of biomarkers to identify patients who will benefit from ICIs. The programmed cell death ligand 1 (PD-L1) expression has been the first biomarker developed. However, its use as a robust predictive biomarker has been limited due to the variability of techniques used, with different antibodies and thresholds. In this context, tumor mutational burden (TMB) has emerged as an additional powerful biomarker based on the observation of successful response to ICIs in solid tumors with high TMB. TMB can be defined as the total number of nonsynonymous mutations per DNA megabases being a mechanism generating neoantigens conditioning the tumor immunogenicity and response to ICIs. However, the latest data provide conflicting results regarding its role as a biomarker. Moreover, considering the results of the recent data, the use of peripheral blood T cell receptor (TCR) repertoire could be a new predictive biomarker. This review summarises recent findings describing the clinical utility of TMB and TCRβ (TCRB) and concludes that immune, neontigen, and checkpoint targeted variables are required in combination for accurately identifying patients who most likely will benefit of ICIs.

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