2023
Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience
Scott S, Marin E, Maples K, Joseph N, Hofmeister C, Gupta V, Dhodapkar M, Kaufman J, Lonial S, Nooka A. Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience. Blood Cancer Journal 2023, 13: 191. PMID: 38114481, PMCID: PMC10730907, DOI: 10.1038/s41408-023-00963-y.Peer-Reviewed Original ResearchProphylactic Tocilizumab to Prevent Cytokine Release Syndrome (CRS) with Teclistamab Administration
Marin E, Scott S, Maples K, Joseph N, Hofmeister C, Gupta V, Dhodapkar M, Kaufman J, Lonial S, Nooka A. Prophylactic Tocilizumab to Prevent Cytokine Release Syndrome (CRS) with Teclistamab Administration. Blood 2023, 142: 2008. DOI: 10.1182/blood-2023-189878.Peer-Reviewed Original ResearchCytokine release syndromeGrade 3 cytokine release syndromeSeverity of CRSB-cell maturation antigenProphylactic cohortRelease syndromeMedian durationRRMM patientsAdditional patientsREMS programT-cell engaging therapiesGrade 1Institutional guidelinesDose of steroidsFirst full doseDays of dischargeEmory University HospitalCD38 monoclonal antibodyUsage of steroidsCellular Therapy criteriaDose delaysNeurotoxicity syndromeOutpatient administrationT cell surfaceTocilizumab groupA phase 2 trial of mosunetuzumab with lenalidomide augmentation as first-line therapy for follicular (FL) and marginal zone lymphoma (MZL).
Olszewski A, Huntington S, Ollila T, Pelcovits A, McMahon J, Yakirevich I, Sturtevant A, Chorzalska A, Morgan J, Dubielecka P. A phase 2 trial of mosunetuzumab with lenalidomide augmentation as first-line therapy for follicular (FL) and marginal zone lymphoma (MZL). Journal Of Clinical Oncology 2023, 41: tps7588-tps7588. DOI: 10.1200/jco.2023.41.16_suppl.tps7588.Peer-Reviewed Original ResearchMarginal zone lymphomaCytokine release syndromeFirst-line therapyCR rateT cell-engaging bispecific antibodiesFirst-line systemic therapyCytotoxic T cell responsesLow-dose lenalidomideComplete response rateFirst-line treatmentLines of therapyPhase 2 trialT-cell depletionT cell immunityT cell responsesHost immune environmentRate of progressionRates of toxicityNovel therapeutic approachesHigh-burden diseasesImmunosuppressive modalitiesRefractory FLRelease syndromeStable diseaseStudy therapyProtracted Pulmonary Inflammation in IFN-gamma Deficient Mice Recovering From Cytokine Release Syndrome
Rajagopalan G, Sun Y, Hu B, Harris Z, Stanely G, Koff J. Protracted Pulmonary Inflammation in IFN-gamma Deficient Mice Recovering From Cytokine Release Syndrome. 2023, a1386-a1386. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a1386.Peer-Reviewed Original ResearchIFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury.
Sun Y, Hu B, Stanley G, Harris ZM, Gautam S, Homer R, Koff JL, Rajagopalan G. IFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury. American Journal Of Respiratory Cell And Molecular Biology 2023, 68: 75-89. PMID: 36125351, PMCID: PMC9817908, DOI: 10.1165/rcmb.2022-0117oc.Peer-Reviewed Original ResearchConceptsCytokine release syndromeAcute lung injuryExtrapulmonary acute lung injuryIFN-γ KO miceIL-17ALung injuryKO miceStaphylococcal enterotoxin BRelease syndromeIL-17A KO miceSevere acute lung injuryAcute respiratory distress syndromeSystemic T cell activationEnterotoxin BAdaptive T lymphocytesDR3 transgenic miceNeutralization of IFNRespiratory distress syndromeHuman leukocyte antigenRole of IFNT cell cytokinesJanus kinase inhibitorS100A8/A9T cell activationALI parameters
2022
Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors
Chen Q, Lu L, Ma W. Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors. Cancers 2022, 14: 5983. PMID: 36497465, PMCID: PMC9739567, DOI: 10.3390/cancers14235983.Peer-Reviewed Original ResearchCAR T-cell therapyT-cell therapyCAR T cellsT cellsSolid tumorsChimeric antigen receptor T-cell therapyAdequate T-cell responsesCytokine release syndromeHalf of patientsT cell responsesTumor antigen targetsRelease syndromeAdoptive immunotherapyClinical efficacyHeterogeneous solid tumorsHematological malignanciesSide effectsTarget antigenAntigen targetsTherapyTumorsCancer treatmentNon-cancer cellsCancer cellsEfficacy
2021
BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?
Allen C, Zeidan AM, Bewersdorf JP. BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML? Life 2021, 11: 465. PMID: 34071099, PMCID: PMC8224808, DOI: 10.3390/life11060465.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaAntibody-based therapiesBispecific antibodiesSide effectsMalignant cellsBispecific T-cell engagersCytokine release syndromeCommon side effectsLeukemia-associated antigensT-cell engagersEarly encouraging resultsRelease syndromeGemtuzumab ozogamicinTreatment landscapeAML treatmentCell engagersAntigen escapeMyeloid leukemiaT cellsImmune responseFuture treatmentTherapyAntibodiesTreatmentCellsA retrospective matched cohort single‐center study evaluating outcomes of COVID‐19 and the impact of immunomodulation on COVID‐19‐related cytokine release syndrome in solid organ transplant recipients
Ringer M, Azmy V, Kaman K, Tang D, Cheung H, Azar MM, Price C, Malinis M. A retrospective matched cohort single‐center study evaluating outcomes of COVID‐19 and the impact of immunomodulation on COVID‐19‐related cytokine release syndrome in solid organ transplant recipients. Transplant Infectious Disease 2021, 23: e13556. PMID: 33378571, PMCID: PMC7883059, DOI: 10.1111/tid.13556.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedCase-Control StudiesCohort StudiesComorbidityCOVID-19COVID-19 Drug TreatmentCytokine Release SyndromeFemaleGlucocorticoidsGraft RejectionHeart TransplantationHospitalizationHumansImmunologic FactorsImmunosuppressive AgentsInterleukin-10Interleukin-6Kidney TransplantationLiver TransplantationMaleMiddle AgedReceptors, Interleukin-2Retrospective StudiesSARS-CoV-2Severity of Illness IndexTreatment OutcomeYoung AdultConceptsCytokine release syndromeBody mass indexNon-SOT patientsSOT groupSOT patientsRelease syndromeInterleukin-6COVID-19-related cytokine release syndromeSoluble interleukin-2 receptor levelsControl groupInterleukin-2 receptor levelsSolid organ transplant patientsSolid organ transplant recipientsImpact of immunomodulationInterleukin-10 levelsOrgan transplant recipientsOrgan transplant patientsCritical care needsMulti-center studyCoronavirus disease 2019COVID-19Interleukin levelsIndex hospitalizationTransplant patientsTransplant recipientsAssociation Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19
Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, Brenner SK, Leonberg-Yoo A, Schenck EJ, Radbel J, Reiser J, Bansal A, Srivastava A, Zhou Y, Finkel D, Green A, Mallappallil M, Faugno AJ, Zhang J, Velez JCQ, Shaefi S, Parikh CR, Charytan DM, Athavale AM, Friedman AN, Redfern RE, Short SAP, Correa S, Pokharel KK, Admon AJ, Donnelly JP, Gershengorn HB, Douin DJ, Semler MW, Hernán MA, Leaf DE, Walther C, Anumudu S, Arunthamakun J, Kopecky K, Milligan G, McCullough P, Nguyen T, Shaefi S, Krajewski M, Shankar S, Pannu A, Valencia J, Waikar S, Kibbelaar Z, Athavale A, Hart P, Upadhyay S, Vohra I, Oyintayo A, Green A, Rachoin J, Schorr C, Shea L, Edmonston D, Mosher C, Shehata A, Cohen Z, Allusson V, Bambrick-Santoyo G, Bhatti N, Mehta B, Williams A, Brenner S, Walters P, Go R, Rose K, Hernán M, Lisk R, Zhou A, Kim E, Chan L, Mathews K, Coca S, Altman D, Saha A, Soh H, Wen H, Bose S, Leven E, Wang J, Mosoyan G, Nadkarni G, Pattharanitima P, Gallagher E, Friedman A, Guirguis J, Kapoor R, Meshberger C, Kelly K, Parikh C, Garibaldi B, Corona-Villalobos C, Wen Y, Menez S, Malik R, Cervantes C, Gautam S, Mallappallil M, Ouyang J, John S, Yap E, Melaku Y, Mohamed I, Bajracharya S, Puri I, Thaxton M, Bhattacharya J, Wagner J, Boudourakis L, Nguyen H, Ahoubim A, Kashani K, Tehranian S, Thomas L, Sirganagari D, Guru P, Zhou Y, Bergl P, Rodriguez J, Shah J, Gupta M, Kumar P, Lazarous D, Kassaye S, Melamed M, Johns T, Mocerino R, Prudhvi K, Zhu D, Levy R, Azzi Y, Fisher M, Yunes M, Sedaliu K, Golestaneh L, Brogan M, Kumar N, Chang M, Thakkar J, Raichoudhury R, Athreya A, Farag M, Schenck E, Cho S, Plataki M, Alvarez-Mulett S, Gomez-Escobar L, Pan D, Lee S, Krishnan J, Whalen W, Charytan D, Macina A, Chaudhry S, Wu B, Modersitzki F, Srivastava A, Leidner A, Martinez C, Kruser J, Wunderink R, Hodakowski A, Velez J, Price-Haywood E, Matute-Trochez L, Hasty A, Mohamed M, Avasare R, Zonies D, Leaf D, Gupta S, Sise M, Newman E, Omar S, Pokharel K, Sharma S, Singh H, Correa S, Shaukat T, Kamal O, Wang W, Yang H, Boateng J, Lee M, Strohbehn I, Li J, Mueller A, Redfern R, Cairl N, Naimy G, Abu-Saif A, Hall D, Bickley L, Rowan C, Madhani-Lovely F, Peev V, Reiser J, Byun J, Vissing A, Kapania E, Post Z, Patel N, Hermes J, Sutherland A, Patrawalla A, Finkel D, Danek B, Arikapudi S, Paer J, Cangialosi P, Liotta M, Radbel J, Puri S, Sunderram J, Scharf M, Ahmed A, Berim I, Vatson J, Anand S, Levitt J, Garcia P, Boyle S, Song R, Arif A, Zhang J, Woo S, Deng X, Katz-Greenberg G, Senter K, Sharshir M, Rusnak V, Ali M, Peters T, Hughes K, Bansal A, Podoll A, Chonchol M, Sharma S, Burnham E, Douin D, Rashidi A, Hejal R, Judd E, Latta L, Tolwani A, Albertson T, Adams J, Chang S, Beutler R, Schulze C, Macedo E, Rhee H, Liu K, Jotwani V, Koyner J, Shah C, Jaikaransingh V, Toth-Manikowski S, Joo M, Lash J, Neyra J, Chaaban N, Elias M, Ahmad Y, Iardino A, Au E, Sharma J, Sosa M, Taldone S, Contreras G, Zerda D, Fornoni A, Gershengorn H, Hayek S, Blakely P, Berlin H, Azam T, Shadid H, Pan M, O’ Hayer P, Meloche C, Feroze R, Padalia K, Bitar A, Leya J, Donnelly J, Admon A, Flythe J, Tugman M, Chang E, Brown B, Leonberg-Yoo A, Spiardi R, Miano T, Roche M, Vasquez C, Bansal A, Ernecoff N, Kapoor S, Verma S, Chen H, Kovesdy C, Molnar M, Azhar A, Hedayati S, Nadamuni M, Shastri S, Willett D, Short S, Renaghan A, Enfield K, Bhatraju P, Malik A, Semler M, Vijayan A, Joy C, Li T, Goldberg S, Kao P, Schumaker G, Goyal N, Faugno A, Hsu C, Tariq A, Meyer L, Kshirsagar R, Jose A, Weiner D, Christov M, Griffiths J, Gupta S, Kapoor A, Wilson P, Arora T, Ugwuowo U. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Internal Medicine 2021, 181: 41-51. PMID: 33080002, PMCID: PMC7577201, DOI: 10.1001/jamainternmed.2020.6252.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdrenal Cortex HormonesAdultAgedAntibodies, Monoclonal, HumanizedAnticoagulantsCohort StudiesCOVID-19COVID-19 Drug TreatmentCritical IllnessEarly Medical InterventionFemaleHospital MortalityHospitalizationHumansIntensive Care UnitsMaleMiddle AgedMortalityOrgan Dysfunction ScoresPatient PositioningProne PositionProportional Hazards ModelsReceptors, Interleukin-6Respiration, ArtificialRespiratory InsufficiencySARS-CoV-2Young AdultConceptsIntensive care unitICU admissionIll patientsCohort studyHazard ratioInverse probability weightingCOVID-19Severe COVID-19 illnessTocilizumab-treated patientsCytokine release syndromeMulticenter cohort studyDay of admissionCox regression modelRandomized clinical trialsCOVID-19 illnessCoronavirus disease 2019Interleukin-6 receptorHospital mortalityRelease syndromeIll adultsCare unitIllness characteristicsClinical trialsTocilizumabEarly treatment
2020
574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation
Schiffer M, Perreault S, McManus D, Foss F, Gowda L, Isufi I, Seropian S, Topal J. 574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation. Open Forum Infectious Diseases 2020, 7: s352-s352. PMCID: PMC7776323, DOI: 10.1093/ofid/ofaa439.768.Peer-Reviewed Original ResearchCytokine release syndromeHaploidentical hematopoietic stem cell transplantationHematopoietic stem cell transplantationFebrile neutropeniaHaplo-HSCTStem cell transplantationRelease syndromeBreakthrough infectionsCell transplantationRecurrent feverEmpiric broad-spectrum antibiotic therapyRates of FNBroad-spectrum antibiotic therapyMulti-drug resistant organismsHaplo-HSCT patientsNon-infectious complicationsPost-transplant cyclophosphamideStem cell infusionBlood culture dataPositive blood culturesBroad-spectrum antibioticsYale New Haven HealthBackground FeverAntibacterial prophylaxisSecondary endpointsOverview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease
Zhou Z, Price CC. Overview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease. Expert Opinion On Investigational Drugs 2020, 29: 1407-1412. PMID: 33094669, DOI: 10.1080/13543784.2020.1840549.BooksConceptsCytokine release syndromeIL-6 inhibitorsRelease syndromeSafety profileInterleukin-6Mild safety profileRandomized clinical trialsTreatment of patientsAvailable clinical dataCOVID-19COVID-19 diseaseCOVID-19 managementNovel coronavirus pneumoniaHyperinflammatory stateClinical outcomesHealthcare burdenClinical trialsClinical dataObservational studyImmune responseLong-term effectsClinical reportsLiterature searchCoronavirus pneumoniaTocilizumabDiagnosis of SARS-CoV-2 infection in the setting of the cytokine release syndrome
Azar MM, Shin JJ, Kang I, Landry M. Diagnosis of SARS-CoV-2 infection in the setting of the cytokine release syndrome. Expert Review Of Molecular Diagnostics 2020, 20: 1087-1097. PMID: 32990479, DOI: 10.1080/14737159.2020.1830760.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Immune profileCOVID-19SARS-CoV-2 infectionCytokine release syndromeAdaptive immune cellsMultiple inflammatory cytokinesSARS-CoV-2 RNAFalse-negative resultsRelease syndromeInfectious complicationsIL-10Laboratory markersD-dimerInflammatory moleculesIP-10IL-6Inflammatory cytokinesMCP-1Acute diagnosisIL-2Immune cellsClinical severityTherapeutic benefitPathogenic contribution“Small” Intestinal Immunopathology Plays a “Big” Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor
Kale SD, Mehrkens BN, Stegman MM, Kastelberg B, Carnes H, McNeill RJ, Rizzo A, Karyala SV, Coutermarsh-Ott S, Fretz JA, Sun Y, Koff JL, Rajagopalan G. “Small” Intestinal Immunopathology Plays a “Big” Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor. Frontiers In Immunology 2020, 11: 1311. PMID: 32676080, PMCID: PMC7333770, DOI: 10.3389/fimmu.2020.01311.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCoronavirus InfectionsCOVID-19Cytokine Release SyndromeCytokinesHLA-DR3 AntigenInterferon-gammaInterleukin-17Intestine, SmallJanus Kinase InhibitorsLymphocyte ActivationMiceMice, KnockoutNitrilesPandemicsPneumonia, ViralPyrazolesPyrimidinesT-Lymphocytes, Helper-InducerConceptsSmall bowel pathologyMultiple organ dysfunctionIL-17A deficiencySmall intestinal immunopathologyCytokine release syndromeToxic shock syndromeBowel pathologyIntestinal immunopathologyRelease syndromeChimeric antigen receptor T-cell therapySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Immune check point inhibitorsHLA-DR3 transgenic miceRespiratory syndrome coronavirus 2HLA-DR3 miceIFN-γ deficiencyCheck point inhibitorsSyndrome coronavirus 2T-cell therapyJAK 1/2 inhibitorJanus kinase inhibitorSmall intestinal tissueCoronavirus disease 2019T cell activationTocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes
Price CC, Altice FL, Shyr Y, Koff A, Pischel L, Goshua G, Azar MM, Mcmanus D, Chen SC, Gleeson SE, Britto CJ, Azmy V, Kaman K, Gaston DC, Davis M, Burrello T, Harris Z, Villanueva MS, Aoun-Barakat L, Kang I, Seropian S, Chupp G, Bucala R, Kaminski N, Lee AI, LoRusso PM, Topal JE, Dela Cruz C, Malinis M. Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes. CHEST Journal 2020, 158: 1397-1408. PMID: 32553536, PMCID: PMC7831876, DOI: 10.1016/j.chest.2020.06.006.Peer-Reviewed Original ResearchConceptsCytokine release syndromeTocilizumab-treated patientsSevere diseaseRelease syndromeTocilizumab treatmentInflammatory biomarkersNonsevere diseaseSoluble IL-2 receptor levelsHigh-sensitivity C-reactive proteinIL-2 receptor levelsConsecutive COVID-19 patientsIL-6 receptor antagonistMechanical ventilation outcomesC-reactive proteinCOVID-19 patientsHigher admission levelsRace/ethnicityMV daysVentilation outcomesAdverse eventsChart reviewClinical responseMedian ageWhite patientsClinical outcomesReal-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab
Badar T, Szabo A, Advani A, Wadleigh M, Arslan S, Khan MA, Aldoss I, Siebenaller C, Schultz E, Hefazi M, Shallis RM, Yurkiewicz I, Podoltsev N, Patel AA, Curran E, Balasubramanian S, Yang J, Mattison RJ, Burkart M, Dinner S, Liedtke M, Litzow MR, Atallah E. Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab. Blood Advances 2020, 4: 2308-2316. PMID: 32453836, PMCID: PMC7252553, DOI: 10.1182/bloodadvances.2019001381.Peer-Reviewed Original ResearchConceptsMedian relapse-free survivalAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationRelapse-free survivalAcute lymphoblastic leukemiaOverall survivalCell transplantationRR diseaseClinical trialsComplete remission/complete remissionRetrospective multicenter cohort analysisB-cell acute lymphoblastic leukemiaB-cell acute lymphocytic leukemia patientsCytokine release syndromeIncomplete count recoveryMulticenter cohort analysisAcute lymphocytic leukemia patientsFavorable prognostic significanceLymphocytic leukemia patientsReal-world outcomesConsolidation therapyMRD negativityPrior therapyRelease syndromeComplete remission
2019
Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy
Abu-Sbeih H, Tang T, Ali F, Luo W, Neelapu S, Westin J, Okhuysen P, Foo W, Curry J, Richards D, Ge P, Wang Y. Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy. American Journal Of Clinical Oncology 2019, 42: 789-796. PMID: 31478934, DOI: 10.1097/coc.0000000000000596.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge DistributionAntineoplastic Combined Chemotherapy ProtocolsAsparaginaseBiopsy, NeedleCohort StudiesCytarabineDaunorubicinFemaleGastric MucosaGastritisGastrointestinal DiseasesHematologic NeoplasmsHumansImmunohistochemistryImmunotherapy, AdoptiveIncidenceMaleMiddle AgedPrognosisReceptors, Chimeric AntigenRetrospective StudiesRisk AssessmentSeverity of Illness IndexSex DistributionThioguanineConceptsChimeric antigen receptor T-cell therapyCytokine release syndromeGastrointestinal adverse eventsGI AEsT-cell therapyRefractory colitisEncephalopathy syndromeRelease syndromeAdverse eventsHematologic malignanciesDiffuse large B-cell lymphomaLarge B-cell lymphomaGastrointestinal tract inflammationGrade 1 diarrheaOnly symptomatic treatmentStandard of careCertain hematologic malignanciesB-cell lymphomaCART infusionAbdominal distensionAbdominal painBloody stoolGastrointestinal symptomsMedian durationExperienced diarrhea
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