2025
Cardiac Magnetic Resonance Imaging in Immune Checkpoint Inhibitor–Related Myocarditis
Hammer M, Tysarowski M, Fuss C, Bader A. Cardiac Magnetic Resonance Imaging in Immune Checkpoint Inhibitor–Related Myocarditis. Echocardiography 2025, 42: e70131. PMID: 40067334, DOI: 10.1111/echo.70131.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsCardiac magnetic resonance imagingMagnetic resonance imagingAssociated with immune-related adverse eventsCardiac immune-related adverse eventsMechanisms of immune checkpoint inhibitorsICI-associated myocarditisICI-related myocarditisResonance imagingPersonalized cancer immunotherapySevere cardiovascular complicationsImmune tolerance pathwayCheckpoint inhibitorsCancer immunotherapyCardiac complicationsCombination therapyTumor cytotoxicityClinical presentationCardiovascular complicationsAdverse eventsTherapeutic efficacyOncological treatmentTherapeutic strategiesMyocarditisAvelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): Long-term outcomes from JAVELIN Bladder 100.
Gupta S, Grivas P, Park S, Petrylak D, Tyroller K, Hoffman J, Bellmunt J. Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): Long-term outcomes from JAVELIN Bladder 100. Journal Of Clinical Oncology 2025, 43: 869-869. DOI: 10.1200/jco.2025.43.5_suppl.869.Peer-Reviewed Original ResearchProgression-free survivalAdvanced urothelial carcinomaBest supportive carePlatinum-based chemotherapyOverall survivalDiabetes mellitusAdverse eventsAssociated with long-term efficacyImmune-related adverse eventsTreatment-related adverse eventsFirst-line maintenanceAssociated with reduced efficacyEfficacy of immunotherapyMedian follow-upProlonged overall survivalLong-term efficacyPresence of DMLong-term outcomesPost hoc exploratory analysisJAVELIN BladderMedian OSMetastatic UCUrothelial carcinomaEligible ptsPrimary endpoint
2024
Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities
Ruddle N. Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities. Methods In Molecular Biology 2024, 2864: 299-312. PMID: 39527229, DOI: 10.1007/978-1-0716-4184-2_16.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsTertiary lymphoid structuresSecondary lymphoid organsTA-TLSSusceptibility to immune-related adverse eventsAssociated with favorable clinical outcomesPositive response to immunotherapyResponse to immunotherapyFavorable clinical outcomesCellular compositionVascular growth factorsAccumulation of lymphoid cellsCheckpoint inhibitorsLymphoid neogenesisLymphoid structuresProcess of lymphoid neogenesisClinical outcomesAdenovirus vectorLymphoid cellsTumor-associatedAdverse eventsTumor environmentOrgan rejectionChronic inflammationSuccessful management of pre-existing psoriatic arthritis through targeting the IL-23/IL-17 axis in cancer patients receiving immune checkpoint inhibitor therapy: a case series
Li Y, Msaouel P, Campbell M, Hwu P, Diab A, Kim S. Successful management of pre-existing psoriatic arthritis through targeting the IL-23/IL-17 axis in cancer patients receiving immune checkpoint inhibitor therapy: a case series. RMD Open 2024, 10: e004308. PMID: 39214611, PMCID: PMC11367333, DOI: 10.1136/rmdopen-2024-004308.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune checkpoint inhibitor therapyAnti-IL-17A antibodyAdverse eventsAnti-PD-1 antibody monotherapyInterleukin (IL)-17/IL-23 axisPsoriatic arthritisImmune checkpoint inhibitor treatmentPD-1 antibody therapyResponse to ICI therapyImmune-related adverse eventsIL-23/IL-17 axisImmune checkpoint inhibitor exposureIL-17/23 axisAnti-CTLA-4Checkpoint inhibitor therapyCell renal cell carcinomaAnti-IL-17AAnti-IL-23 antibodyAssociated with adverse eventsPre-existing psoriasisAnti-tumor efficacyIL-23/IL-17Renal cell carcinomaICI therapyTofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study
Liu Q, Liu M, Zou Z, Lin J, Zhang N, Zhao L, Zhou J, Zhou H, Zhou X, Jiao X, Yu Y, Liu T. Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study. Journal Of Translational Medicine 2024, 22: 803. PMID: 39210332, PMCID: PMC11360683, DOI: 10.1186/s12967-024-05617-6.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsManagement of immune-related adverse eventsOverall survivalTofacitinib treatmentAdverse eventsTreatment of immune-related adverse eventsCancer patientsImmune checkpoint inhibitor initiationImmune checkpoint inhibitor myocarditisSteroid-resistant casesTreated with tofacitinibClinical remission rateResultsFifty-three patientsSafety of tofacitinibCardiac troponin TLife-threatening casesMulti-center observational studyAnti-tumor activityMultiple autoimmune diseasesBackgroundTreatment strategiesCheckpoint inhibitorsMedian OSSteroid taperCancer immunotherapyThyroid dysfunction caused by immune checkpoint inhibitors improves cancer outcomes.
García-Goñi M, Vázquez Gutiérrez B, Sanmamed M, Martín-Algarra S, Luis Pérez-Gracia J, Olmedo M, Chumbiauca E, Martín-Calvo N, Galofré J. Thyroid dysfunction caused by immune checkpoint inhibitors improves cancer outcomes. Endocrine Related Cancer 2024, 31 PMID: 39013402, DOI: 10.1530/erc-24-0064.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune-related adverse eventsRisk of progressionOverall survivalPrimary tumorThyroid dysfunctionPatients treated with immune checkpoint inhibitorsCancer patients treated with immune checkpoint inhibitorsAssociated with higher ORRImmune checkpoint inhibitor regimenTreated with atezolizumabLonger overall survivalCox proportional hazards modelsResponse to treatmentProbability of recurrenceMultivariable-adjusted regressionRisk of mortalityProportional hazards modelIndependent of ageCheckpoint inhibitorsRECIST v1.1Higher ORRCombination therapyUrothelial cancerClinical presentation22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)
Saad E, Mehrabad E, Labaki C, Saliby R, Semaan K, Eid M, Machaalani M, Chehade R, Nawfal R, Sun M, Sharon E, Shah P, Vemula S, Gupta S, Braun D, Van Allen E, Gusev A, Choueiri T. 22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs). The Oncologist 2024, 29: s1-s2. PMCID: PMC11301885, DOI: 10.1093/oncolo/oyae181.003.Peer-Reviewed Original ResearchImmune-related adverse eventsMetastatic non-small cell lung cancerMetastatic renal cell carcinomaImmune checkpoint inhibitorsProgression-free survivalWhole-exome sequencingRecurrent grade 2Overall survivalGrade 2Interleukin-7Single nucleotide polymorphismsNivolumab armPembrolizumab armSomatic alterationsAdverse eventsTreatment armsPrediction of immune-related adverse eventsCumulative rates of adverse eventsTumor whole-exome sequencingRates of grade 2Non-small cell lung cancerGermline single nucleotide polymorphismsClinical trials of patientsAssociated with significantly higher ratesPD-1 inhibitorsPeripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer
Foldi J, Blenman K, Marczyk M, Gunasekharan V, Polanska A, Gee R, Davis M, Kahn A, Silber A, Pusztai L. Peripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 369-377. PMID: 39002068, DOI: 10.1007/s10549-024-07426-3.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerAssociated with pathological responsePathological complete responseNeoadjuvant chemotherapyCytokine levelsPathological responseAdverse eventsBreast cancerEarly-stage triple-negative breast cancerPatients treated with immune checkpoint inhibitorsB cell clonal expansionMeasured serum cytokine levelsImmune checkpoint inhibitorsGM-CSF levelsPeripheral blood cytokine levelsBlood cytokine levelsSerum cytokine levelsB cell receptorMagnetic bead panelBenjamini-Hochberg correctionSample of patientsImmunoSEQ platformCheckpoint inhibitorsComplete responseIncidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial.
Nanda R, Cohen R, Quandt Z, Basu A, Yau C, Chien A, Pusztai L, Han H, Stringer-Reasor E, Isaacs C, Hershman D, Shatsky R, Perlmutter J, Yee D, DeMichele A, van 't Veer L, Hylton N, Esserman L, Rugo H. Incidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial. Journal Of Clinical Oncology 2024, 42: 584-584. DOI: 10.1200/jco.2024.42.16_suppl.584.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsEarly breast cancerIncidence of AIAdrenal insufficiencyI-SPY2Advanced diseaseBreast cancerRisk of immune-related adverse eventsHigh-risk early breast cancerImmune checkpoint inhibitor doseTriple-negative breast cancerAnti-LAG-3Approval of pembrolizumabEvaluate novel agentsICI-based therapyWeekly x 4Rate of adrenal insufficiencyPhase 2 trialI-SPY2 trialTime to onsetAge of ptsCheckpoint inhibitorsNeoadjuvant settingWeekly paclitaxelAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Alter R, Bilen M, Braun D, Einstein D, Haas N, Herchenhorn D, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Signoretti S, CHOUEIRI T, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps4614-tps4614. DOI: 10.1200/jco.2024.42.16_suppl.tps4614.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAssociated with increased presenceThe Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases
Pach J, Valido K, Belzer A, Leventhal J. The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases. American Journal Of Clinical Dermatology 2024, 25: 595-607. PMID: 38767827, DOI: 10.1007/s40257-024-00866-z.Peer-Reviewed Original ResearchCutaneous immune-related adverse eventsImmune-related adverse eventsAdverse eventsAntitumor responseBiological agentsHigh-dose systemic corticosteroidsSevere cutaneous adverse reactionsImmune checkpoint inhibitorsStevens-Johnson syndromeCutaneous adverse reactionsAdverse event patternEnglish-language literatureTransient acantholytic dermatosisTreating high-gradeSpectrum of dermatologic manifestationsCheckpoint inhibitorsSystemic corticosteroidsCorticosteroid-sparingImmunobullous disordersPsoriasiform eruptionLichenoid reactionsEczematous dermatitisLichenoid eruptionDermatological manifestationsHigh-gradeMIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy
Fey R, Nichols R, Tran T, Vandenbark A, Kulkarni R. MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy. Cancers 2024, 16: 1773. PMID: 38730725, PMCID: PMC11082995, DOI: 10.3390/cancers16091773.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune-related adverse events developmentResponse to ICB therapyImmune checkpoint blockade therapyImmune checkpoint blockadePredictive biomarkersICB therapyCheckpoint blockade therapySerum MIF levelsBlockade therapyCheckpoint blockadeMIF levelsMalignant melanomaTreatment resistanceSolid tumorsAdverse eventsAutoimmune diseasesContext of cancerPrognostic biomarkerCancer progressionCognate receptor CD74Receptor CD74TherapyCD74CancerAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Bilen M, Braun D, Einstein D, Haas N, Hammers H, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Choueiri T, Signoretti S, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps492-tps492. DOI: 10.1200/jco.2024.42.4_suppl.tps492.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAnti-tumor activityComparing the rate of immunotherapy treatment change due to toxicity by sex
Chua K, Kronstedt S, Kaldany A, Srivastava A, Doppalapudi S, Liu H, Tarhini A, Gatti‐Mays M, Gaughan E, Hu‐Lieskovan S, Aljumaily R, Nepple K, Schneider B, Sterling J, Singer E. Comparing the rate of immunotherapy treatment change due to toxicity by sex. Cancer Reports 2024, 7: e1932. PMID: 38189893, PMCID: PMC10849926, DOI: 10.1002/cnr2.1932.Peer-Reviewed Original ResearchConceptsImmuno-oncology therapiesChronic obstructive pulmonary diseaseTreatment discontinuation rateDiscontinuation ratesNo significant differenceImmune-related adverse eventsTreatment due to toxicityTreatment changesTreatment-related toxicityPatients changed treatmentSignificant differenceFrequent treatment changesAssociated with chronic obstructive pulmonary diseaseMultivariate logistic regressionObstructive pulmonary diseaseChi-square testState Cancer CenterPrimary endpointAdverse eventsIO treatmentAutoimmune diseasesCancer CenterPulmonary diseasePatientsCancer typesThe Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers
Mustafa S, Jansen C, Jani Y, Evans S, Zhuang T, Brown J, Nazha B, Master V, Bilen M. The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers. Biomarker Insights 2024, 19: 11772719241254179. PMID: 38827239, PMCID: PMC11143877, DOI: 10.1177/11772719241254179.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsResponse to immunotherapyAdverse eventsTreatment of genitourinary malignanciesImmune checkpoint blockadeSelection of therapySignificant side effectsCheckpoint blockadeCheckpoint inhibitorsGU malignanciesGenitourinary malignanciesPatient tumorsTreatment landscapeReview of biomarkersGenitourinary cancersGU tumorsPreclinical studiesPrognostic toolSide effectsTherapyBiomarker developmentTumorPatientsImmunotherapy
2023
CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment
Muthana M, Du X, Liu M, Wang X, Wu W, Ai C, Su L, Zheng P, Liu Y. CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment. ELife 2023, 12 DOI: 10.7554/elife.87281.3.Peer-Reviewed Original ResearchImmune-related adverse eventsB-cell depletionB cellsT cellsSevere immune-related adverse eventsCTLA-4 antibody ipilimumabRegulatory T cell impairmentEffector memory T cellsAnti-TNF-alpha antibodyCTLA-4 deficiencyAnti-CTLA-4CD8 T cellsMemory T cellsRegulatory T cellsT cell impairmentPeripheral B cellsB cell lossReduced peripheral B cellsSeveral autoimmune diseasesKnock-in miceAntibody-drug conjugatesAntibody ipilimumabCombination immunotherapyAutoimmune cytopeniasCTLA-4CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment
Muthana M, Du X, Liu M, Wang X, Wu W, Ai C, Su L, Zheng P, Liu Y. CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment. ELife 2023, 12: rp87281. PMID: 38127423, PMCID: PMC10735222, DOI: 10.7554/elife.87281.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsB-cell depletionB cellsT cellsSevere immune-related adverse eventsCTLA-4 antibody ipilimumabRegulatory T cell impairmentEffector memory T cellsAnti-TNF-alpha antibodyAnti-CTLA-4CTLA-4 deficiencyFoxP3<sup>+</sup> TregsCD8 T cellsT cell impairmentMemory T cellsRegulatory T cellsPeripheral B cellsB cell lossReduced peripheral B cellsSeveral autoimmune diseasesKnock-in miceAntibody-drug conjugatesAntibody ipilimumabCombination immunotherapyAutoimmune cytopeniasBlinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study
Webster J, Luskin M, Rimando J, Blackford A, Zeidan A, Sharon E, Streicher H, DeAngelo D, Luznik L, Gojo I. Blinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study. Blood 2023, 142: 966. DOI: 10.1182/blood-2023-191109.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMixed phenotype acute leukemiaRelapse-free survivalOverall survivalAcute lymphoblastic leukemiaComplete remissionPD-1Checkpoint inhibitorsExtramedullary diseaseAdverse eventsBM blastsGrade 3Positive B-cell acute lymphoblastic leukemiaResponse rateImmune-related adverse eventsB-cell acute lymphoblastic leukemiaMulti-center phase IPhase IDose-escalation schemaNon-hematologic toxicitiesMedian overall survivalDose-escalation studyPD-L1 expressionDuration of responseT cell subpopulations1893P Immune-related adverse events from contemporary first-line combination therapies in metastatic renal cell carcinoma: Results from the IMDC
Navani V, Lemelin A, Powles T, Liow E, Wong S, Meza L, Ebrahimi H, Saliby R, Saad E, Yuasa T, Wood L, Kollmannsberger C, Graham J, North S, Basappa N, Donskov F, Rodriguez C, Lalani A, Choueiri T, Heng D. 1893P Immune-related adverse events from contemporary first-line combination therapies in metastatic renal cell carcinoma: Results from the IMDC. Annals Of Oncology 2023, 34: s1018-s1019. DOI: 10.1016/j.annonc.2023.09.1123.Peer-Reviewed Original ResearchNUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma
Sim H, Wachsmuth L, Barnes E, Yip S, Koh E, Hall M, Jennens R, Ashley D, Verhaak R, Heimberger A, Rosenthal M, Hovey E, Ellingson B, Tognela A, Gan H, Wheeler H, Back M, McDonald K, Long A, Cuff K, Begbie S, Gedye C, Mislang A, Le H, Johnson M, Kong B, Simes J, Lwin Z, Khasraw M. NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma. Neuro-Oncology Advances 2023, 5: vdad124. PMID: 37841696, PMCID: PMC10576515, DOI: 10.1093/noajnl/vdad124.Peer-Reviewed Original ResearchExperimental armStandard armOverall survivalAdverse eventsGrade-3 immune-related adverse eventImmune-related adverse eventsUnexpected serious adverse eventsRandomized phase II studyRandomized phase II trialCombination of nivolumabMedian overall survivalPhase II studySerious adverse eventsNew safety signalsOS hazard ratioPhase II trialPhase III trialsAdjuvant nivolumabImmunologic rationaleII trialHazard ratioII studyIII trialsOlder patientsImmunotherapy trials
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