22 results on '"Santomasso, B."'
Search Results
2. INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2
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Einsele, H, primary, Parekh, S, additional, Madduri, D, additional, Santomasso, B, additional, Pérez-Larraya, JG, additional, Donk, NWV, additional, Arnulf, B, additional, Mateos, M, additional, Braganca, KC, additional, Varsos, H, additional, Carrasco-Alfonso, MJ, additional, Akram, M, additional, Lendvai, N, additional, Jackson, CC, additional, Olyslager, Y, additional, Zudaire, E, additional, Li, C, additional, Geng, D, additional, Jakubowiak, A, additional, and Cohen, A, additional
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- 2021
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3. PREDICTORS FOR NEUROTOXICITY on day of infusion of chimeric antigen receptor (CAR) T cells using discovery proteomics platform
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Lakkaraja, M., primary, Hosszu, K., additional, Mcavoy, D., additional, Mauguen, A., additional, Purdon, T.J., additional, Auchincloss, T., additional, Klein, E., additional, Khakoo, Y., additional, Santomasso, B., additional, Senechal, B., additional, Riviere, I., additional, Sadelain, M., additional, Curran, K.J., additional, Park, J., additional, Brentjens, R.J., additional, and Boelens, J.J., additional
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- 2021
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4. PHASE I CLINICAL TRIAL OF CD19-TARGETED 19-28Z/4-1BBL “ARMORED” CAR T CELLS IN PATIENTS WITH RELAPSED OR REFRACTORY NHL AND CLL INCLUDING RICHTER TRANSFORMATION
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Batlevi, C.L., primary, Palomba, M.L., additional, Park, J., additional, Mead, E., additional, Santomasso, B., additional, Riviere, I., additional, Wang, X., additional, Senechal, B., additional, Furman, R., additional, Yang, J., additional, Kane, P., additional, Hall, M., additional, Bernal, Y., additional, Lund, N., additional, Diamonte, C., additional, Pineda, J., additional, Halton, E., additional, Moskowitz, C., additional, Younes, A., additional, Sadelain, M., additional, and Brentjens, R., additional
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- 2019
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5. CR4 RESOURCE UTILIZATION WITHIN 30 DAYS OF CAR T CELLS FOR HEMATOLOGIC MALIGNANCIES
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Shah, G., primary, Park, J., additional, Sauter, C., additional, Duck, E., additional, Halton, E., additional, Batlevi, C., additional, Palomba, M.L., additional, Younes, A., additional, Geyer, M., additional, Smith, E., additional, Santomasso, B., additional, Perales, M.A., additional, Sabatini, P., additional, Giralt, S., additional, Brenjtens, R., additional, and Bach, P.B., additional
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- 2019
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6. G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator
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Bais, C., Santomasso, B., Coso, O., Arvanitakis, L., Raaka, Eg, J Silvio Gutkind, Asch, As, Cesarman, E., Gerhengorn, Mc, and Mesri, Ea
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Multidisciplinary - Published
- 1998
7. 525 - Immunotherapy: DISCOVERY PROTEOMICS FOR ANALYTES TO PREDICT CYTOKINE RELEASE SYNDROME ON DAY OF INFUSION OF CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS.
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Lakkaraja, M., Hosszu, K., Mcavoy, D., Mauguen, A., Purdon, T.J., Auchincloss, T., Klein, E., Khakoo, Y., Santomasso, B., Senechal, B., Riviere, I., Sadelain, M., Curran, K.J., Park, J., Brentjens, R.J., and Boelens, J.J.
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CYTOKINE release syndrome , *CHIMERIC antigen receptors , *IMMUNOTHERAPY , *PROTEOMICS , *T cells , *CYTOTOXIC T cells - Published
- 2022
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8. CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results.
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Park JH, Nath K, Devlin SM, Sauter CS, Palomba ML, Shah G, Dahi P, Lin RJ, Scordo M, Perales MA, Shouval R, Tomas AA, Cathcart E, Mead E, Santomasso B, Holodny A, Brentjens RJ, Riviere I, and Sadelain M
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- Humans, Adult, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Interleukin 1 Receptor Antagonist Protein adverse effects, Antigens, CD19, Neurotoxicity Syndromes etiology, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
In preclinical models, anakinra, an IL-1 receptor antagonist (IL-1Ra), reduced immune effector cell-associated neurotoxicity syndrome (ICANS) without compromising anti-CD19 chimeric antigen receptor (CAR) T-cell efficacy. We initiated a phase 2 clinical trial of anakinra in patients with relapsed/refractory large B-cell lymphoma and mantle cell lymphoma treated with commercial anti-CD19 CAR T-cell therapy. Here we report a non-prespecified interim analysis reporting the final results from cohort 1 in which patients received subcutaneous anakinra from day 2 until at least day 10 post-CAR T-cell infusion. The primary endpoint was the rate of severe (grade ≥3) ICANS. Key secondary endpoints included the rates of all-grade cytokine release syndrome (CRS) and ICANS and overall disease response. Among 31 treated patients, 74% received axicabtagene ciloleucel, 13% received brexucabtagene ciloleucel and 4% received tisagenlecleucel. All-grade ICANS occurred in 19%, and severe ICANS occurred in 9.7% of patients. There were no grade 4 or 5 ICANS events. All-grade CRS occurred in 74%, and severe CRS occurred in 6.4% of patients. The overall disease response rate was 77% with 65% complete response rate. These initial results show that prophylactic anakinra resulted in a low incidence of ICANS in patients with lymphoma receiving anti-CD19 CAR T-cell therapy and support further study of anakinra in immune-related neurotoxicity syndromes., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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9. Reply to M.B. Abid.
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Santomasso B, Ghosh M, Schneider B, and Bollin K
- Abstract
Competing Interests: Bianca SantomassoConsulting or Advisory Role: Celgene, Janssen, Legend Biotech, Incyte, In8BioResearch Funding: ADC Therapeutics (Inst) Monalisa GhoshResearch Funding: Novartis (Inst), Celgene (Inst) Bryan SchneiderResearch Funding: Merck Kathryn BollinConsulting or Advisory Role: Iovance BiotherapeuticsNo other potential conflicts of interest were reported.
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- 2022
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10. Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology.
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Thompson JA, Schneider BJ, Brahmer J, Achufusi A, Armand P, Berkenstock MK, Bhatia S, Budde LE, Chokshi S, Davies M, Elshoury A, Gesthalter Y, Hegde A, Jain M, Kaffenberger BH, Lechner MG, Li T, Marr A, McGettigan S, McPherson J, Medina T, Mohindra NA, Olszanski AJ, Oluwole O, Patel SP, Patil P, Reddy S, Ryder M, Santomasso B, Shofer S, Sosman JA, Wang Y, Zaha VG, Lyons M, Dwyer M, and Hang L
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- Humans, Immune Checkpoint Inhibitors, Immunologic Factors therapeutic use, Immunotherapy adverse effects, Immunotherapy methods, Medical Oncology, Neoplasms drug therapy
- Abstract
The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.
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- 2022
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11. Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells.
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Pennisi M, Sanchez-Escamilla M, Flynn JR, Shouval R, Alarcon Tomas A, Silverberg ML, Batlevi C, Brentjens RJ, Dahi PB, Devlin SM, Diamonte C, Giralt S, Halton EF, Jain T, Maloy M, Mead E, Palomba ML, Ruiz J, Santomasso B, Sauter CS, Scordo M, Shah GL, Park JH, Yanez San Segundo L, and Perales MA
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- Cytokine Release Syndrome, Humans, T-Lymphocytes, Hematopoietic Stem Cell Transplantation, Neurotoxicity Syndromes, Receptors, Chimeric Antigen
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Patients who develop chimeric antigen receptor (CAR) T-cell-related severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) exhibit hemodynamic instability and endothelial activation. The EASIX (Endothelial Activation and Stress Index) score (lactate dehydrogenase [LDH; U/L] × creatinine [mg/dL]/platelets [PLTs; 109 cells/L]) is a marker of endothelial damage that correlates with outcomes in allogeneic hematopoietic cell transplantation. Elevated LDH and low PLTs have been associated with severe CRS and ICANS, as has C-reactive protein (CRP), while increased creatinine is seen only in a minority of advanced severe CRS cases. We hypothesized that EASIX and 2 new modified EASIX formulas (simplified EASIX, which excludes creatinine, and modified EASIX [m-EASIX], which replaces creatinine with CRP [mg/dL]), calculated peri-CAR T-cell infusion, would be associated with development of severe (grade ≥ 3) CRS and ICANS. We included 118 adults, 53 with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 65 with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel or tisagenlecleucel. The 3 formulas showed similar predictive power for severe CRS and ICANS. However, low PLTs and high CRP values were the only variables individually correlated with these toxicities. Moreover, only m-EASIX was a significant predictor of disease response. m-EASIX could discriminate patients who subsequently developed severe CRS preceding the onset of severe symptoms (area under the curve [AUC] at lymphodepletion, 80.4%; at day -1, 73.0%; and at day +1, 75.4%). At day +3, it also had high discriminatory ability for severe ICANS (AUC, 73%). We propose m-EASIX as a clinical tool to potentially guide individualized management of patients at higher risk for severe CAR T-cell-related toxicities., (© 2021 by The American Society of Hematology.)
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- 2021
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12. The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy.
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Garcia-Recio M, Wudhikarn K, Pennisi M, Alonso-Trillo R, Flynn J, Shouval R, Afuye AO, Silverberg ML, Batlevi CW, Dahi P, Devlin S, Giralt SA, Halton E, Ruiz J, Maloy M, Mead E, Palomba ML, Santomasso B, Sauter CS, Scordo M, Shah GL, and Perales MA
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- Cell- and Tissue-Based Therapy, Humans, Immunotherapy, Adoptive, Prognosis, Lymphoma, Large B-Cell, Diffuse therapy, Receptors, Chimeric Antigen
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CD19-targeted chimeric antigen receptor (CAR) T cells have shown excellent activity against relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). CAR T cell therapy is associated with early toxicities, including cytokine release syndrome and neurotoxicity. The incidence and severity of these toxicities has been associated in part with baseline disease and patient characteristics, which also may impact overall survival (OS) and progression-free survival (PFS). However, there are limited data on patient selection and how to better predict toxicities or outcomes. Indexes used in patients with DLBCL, such as the International Prognostic Index (IPI and age-adjusted IPI [aaIPI]) and in transplantation recipients, such as the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), have not been evaluated in this setting. Here we evaluated 4 indices- IPI, aaIPI, HCT-CI, and the Charlson Comorbidity Index (CCI)-and their associations with early CAR T cell related-toxicities and outcomes. We demonstrated an association between high-risk IPI or aaIPI and inferior PFS in patients with R/R DLBCL treated with CAR T cell therapy. We also found an association between aaIPI and IPI with OS and neurotoxicity, respectively. CCI was not associated with toxicities or outcomes, and owing to the small sample size, we could not draw a conclusion regarding associations with the HCT-CI. Both the IPI and aaIPI are widely used tools that can now provide better information to guide selection of patients who would best benefit from CD19 CAR T cell therapy., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2021
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13. Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients.
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Remsik J, Wilcox JA, Babady NE, McMillen TA, Vachha BA, Halpern NA, Dhawan V, Rosenblum M, Iacobuzio-Donahue CA, Avila EK, Santomasso B, and Boire A
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- Angiotensin-Converting Enzyme 2 metabolism, Brain diagnostic imaging, Brain pathology, COVID-19 epidemiology, Cerebrospinal Fluid Proteins analysis, Comorbidity, Cytokines cerebrospinal fluid, Humans, Neoplasms complications, Neoplasms epidemiology, Neuroimaging, Brain Diseases etiology, COVID-19 complications, Inflammation Mediators cerebrospinal fluid, Neoplasms virology
- Abstract
SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection., Competing Interests: Declaration of interests A.B. is an inventor on United States Provisional Patent Application no. 62/258,044 “Modulating Permeability of The Blood Cerebrospinal Fluid Barrier.” A.B. is an unpaid member of the Scientific Advisory Board of EVREN Technologies. B.S. is a paid consultant for Kite Gilead, Juno/Celgene, Janssen, and In8bio. Other authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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14. Clinical trial of proton craniospinal irradiation for leptomeningeal metastases.
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Yang TJ, Wijetunga NA, Yamada J, Wolden S, Mehallow M, Goldman DA, Zhang Z, Young RJ, Kris MG, Yu HA, Seidman AD, Gavrilovic IT, Lin A, Santomasso B, Grommes C, Piotrowski AF, Schaff L, Stone JB, DeAngelis LM, Boire A, and Pentsova E
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- Humans, Prospective Studies, Protons, Craniospinal Irradiation adverse effects, Meningeal Carcinomatosis, Proton Therapy
- Abstract
Background: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors., Methods: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS)., Results: We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months., Conclusion: Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2021
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15. Inflammatory leptomeningeal cytokines mediate delayed COVID-19 encephalopathy.
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Remsik J, Wilcox JA, Babady NE, McMillen T, Vachha BA, Halpern NA, Dhawan V, Rosenblum M, Iacobuzio-Donahue CA, Avila EK, Santomasso B, and Boire A
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SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction. Here we show that a particularly vulnerable population with neurologic manifestations of COVID-19 harbor an influx of inflammatory cytokines within the cerebrospinal fluid in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease models. Levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from the acute respiratory infection. These prolonged neurologic sequelae following a systemic cytokine release syndrome lead to long-term neurocognitive dysfunction with a wide range of phenotypes.
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- 2020
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16. NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020.
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Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, Budde LE, Costa L, Davies M, Dunnington D, Ernstoff MS, Frigault M, Kaffenberger BH, Lunning M, McGettigan S, McPherson J, Mohindra NA, Naidoo J, Olszanski AJ, Oluwole O, Patel SP, Pennell N, Reddy S, Ryder M, Santomasso B, Shofer S, Sosman JA, Wang Y, Weight RM, Johnson-Chilla A, Zuccarino-Catania G, and Engh A
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- Humans, Immunotherapy methods, Antineoplastic Agents, Immunological adverse effects, Neoplasms drug therapy
- Abstract
The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor-related diarrhea/colitis and cardiovascular irAEs.
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- 2020
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17. Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy.
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Chen X, Haggiagi A, Tzatha E, DeAngelis LM, and Santomasso B
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- Adult, Aged, Aged, 80 and over, Axons physiology, Demyelinating Diseases diagnosis, Demyelinating Diseases etiology, Electrodiagnosis methods, Female, Humans, Male, Middle Aged, Motor Neurons physiology, Neural Conduction, Neuromuscular Junction physiopathology, Polyneuropathies diagnosis, Polyneuropathies etiology, Antineoplastic Agents, Immunological adverse effects, Demyelinating Diseases physiopathology, Polyneuropathies physiopathology
- Abstract
Objective: To report the electrodiagnostic features of immune checkpoint inhibitor (ICI)-related neuropathy., Methods: We retrospectively reviewed clinical presentations and electrodiagnostic features of 23 patients studied after receiving immune checkpoint inhibitors (ICIs). The presentations for electrodiagnostic evaluation included an acute neuropathy or neuromuscular junction disorder. We applied established electrodiagnostic criteria for polyneuropathy and acute demyelinating neuropathy., Results: We identified acute demyelinating neuropathy (13 cases), axonal sensory motor neuropathy (5), pure sensory neuropathy (4) and mononeuropathy (1). 13 patients had acute demyelinating neuropathy confirmed by demonstrating demyelination in 2 or more nerves; 3 additional patients had demyelination in only one nerve. Analysis of motor nerve conduction parameters revealed demyelination involving median and ulnar nerve distal motor latencies as well as median, ulnar and peroneal nerve conduction velocities. Conduction block was found in median, ulnar and peroneal nerves. The remaining one-third patients without demyelination had acute painful axonal neuropathy. Coexisting myopathic changes (6) and neuromuscular junction dysfunction (4) were also identified., Conclusions: Our findings suggest that, while immune-mediated motor nerve demyelination is the primary underlying mechanism of ICI-related neuropathy, axonal painful neuropathy can also be an important presentation. Early recognition and effective intervention may reduce morbidity and permanent disability., Significance: Electrophysiological studies might be useful in the evaluation of ICI-related neuropathy., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
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- 2019
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18. Management of Immunotherapy-Related Toxicities, Version 1.2019.
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Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, Budde LE, Costa L, Davies M, Dunnington D, Ernstoff MS, Frigault M, Hoffner B, Hoimes CJ, Lacouture M, Locke F, Lunning M, Mohindra NA, Naidoo J, Olszanski AJ, Oluwole O, Patel SP, Reddy S, Ryder M, Santomasso B, Shofer S, Sosman JA, Wahidi M, Wang Y, Johnson-Chilla A, and Scavone JL
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- Antineoplastic Agents, Immunological therapeutic use, Disease Management, Drug-Related Side Effects and Adverse Reactions etiology, Humans, Molecular Targeted Therapy methods, Neoplasms drug therapy, Neoplasms etiology, Antineoplastic Agents, Immunological adverse effects, Drug-Related Side Effects and Adverse Reactions diagnosis, Drug-Related Side Effects and Adverse Reactions therapy, Molecular Targeted Therapy adverse effects, Neoplasms complications
- Abstract
The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit NCCN.org.
- Published
- 2019
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19. The Other Side of CAR T-Cell Therapy: Cytokine Release Syndrome, Neurologic Toxicity, and Financial Burden.
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Santomasso B, Bachier C, Westin J, Rezvani K, and Shpall EJ
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- Disease Management, Genetic Engineering, Hematologic Neoplasms immunology, Hematologic Neoplasms therapy, Humans, Immunotherapy, Adoptive methods, Nervous System Diseases diagnosis, Nervous System Diseases epidemiology, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell metabolism, Receptors, Chimeric Antigen genetics, Severity of Illness Index, T-Lymphocytes immunology, T-Lymphocytes metabolism, Treatment Outcome, Cost of Illness, Hematologic Neoplasms complications, Hematologic Neoplasms epidemiology, Immunotherapy, Adoptive adverse effects, Nervous System Diseases etiology
- Abstract
Immune effector cells, including T cells and natural killer cells, which are genetically engineered to express a chimeric antigen receptor (CAR), constitute a powerful new class of therapeutic agents to treat patients with hematologic malignancies. Several CAR T-cell trials have shown impressive remission rates in patients with relapsed/refractory hematologic cancers. Although the clinical responses of these agents in hematologic malignancies have been very encouraging, they have also produced substantial morbidity and occasionally mortality resulting from toxicity. With more experience and collaboration, hopefully the toxicities and the costs will come down, increasing the availability of CAR T cells to patients in need.
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- 2019
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20. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.
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Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, Roshal M, Maslak P, Davila M, Brentjens RJ, and Sadelain M
- Subjects
- Adult, Aged, Cytokines metabolism, Follow-Up Studies, Humans, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Recurrence, Remission Induction, Survival Analysis, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Receptors, Antigen, T-Cell therapeutic use, T-Lymphocytes immunology
- Abstract
Background: CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients., Methods: We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics., Results: A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden., Conclusions: In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069 .).
- Published
- 2018
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21. Temporal lobe meningioma with ipsilateral herpes simplex encephalitis.
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Diamond EL, Hatzoglou V, Santomasso B, Rosenblum M, and Pentsova E
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- 2014
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22. Tolerance to the neuron-specific paraneoplastic HuD antigen.
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DeLuca I, Blachère NE, Santomasso B, and Darnell RB
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- Adoptive Transfer, Animals, Autoimmunity, Bone Marrow Cells cytology, CD8-Positive T-Lymphocytes metabolism, Epitopes chemistry, Kidney metabolism, Mice, Mice, Inbred C57BL, Spleen cytology, Brain metabolism, ELAV Proteins metabolism, Lung Neoplasms metabolism, Neurons metabolism, Small Cell Lung Carcinoma metabolism
- Abstract
Experiments dating back to the 1940's have led to the hypothesis that the brain is an immunologically privileged site, shielding its antigens from immune recognition. The paraneoplastic Hu syndrome provides a powerful paradigm for addressing this hypothesis; it is believed to develop because small cell lung cancers (SCLC) express the neuron-specific Hu protein. This leads to an Hu-specific tumor immune response that can develop into an autoimmune attack against neurons, presumably when immune privilege in the brain is breached. Interestingly, all SCLC express the onconeural HuD antigen, and clinically useful tumor immune responses can be detected in up to 20% of patients, yet the paraneoplastic neurologic syndrome is extremely rare. We found that HuD-specific CD8+ T cells are normally present in the mouse T cell repertoire, but are not expanded upon immunization, although they can be detected after in vitro expansion. In contrast, HuD-specific T cells could be directly activated in HuD null mice, without the need for in vitro expansion. Taken together, these results demonstrate robust tolerance to the neuronal HuD antigen in vivo, and suggest a re-evaluation of the current concept of immune privilege in the brain.
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- 2009
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