2024
Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study
Iyer S, Sica R, Ho P, Prica A, Zain J, Foss F, Hu B, Beitinjaneh A, Weng W, Kim Y, Khodadoust M, Huen A, Williams L, Ma A, Huang E, Ganpule A, Nagar S, Sripakdeevong P, Cullingford E, Karnik S, Dequeant M, Patel J, He X, Li Z, He Q, Mendonez J, Keegan A, Horwitz S. Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. The Lancet Oncology 2024 PMID: 39617017, DOI: 10.1016/s1470-2045(24)00508-4.Peer-Reviewed Original ResearchT-cell lymphomaPeripheral T-cell lymphomaCutaneous T-cell lymphomaRefractory T-cell lymphomaEastern Cooperative Oncology GroupChimeric antigen receptorCytokine release syndromeCAR+ T cellsSerious adverse eventsAdverse eventsT cellsOpen-labelRefractory peripheral T-cell lymphomaAllogeneic chimeric antigen receptorHealthy donor T cellsRefractory T-cell malignanciesCAR-T cell therapyMedian patient follow-upIncidence of adverse eventsDonor T cellsObjective response rateSystemic therapy linesDose-limiting toxicityT-cell therapyDose-escalation studyGlobal outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: Results from PETAL consortium
Han J, Koh M, Boussi L, Sorial M, McCabe S, Peng L, Singh S, Eche-Ugwu I, Gabler J, Fernandez Turizo M, MacVicar C, Garg A, Disciullo A, Chopra K, Lenart A, Nwodo E, Barnes J, Koh M, Miranda E, Chiattone C, Stuver R, Horwitz S, Merrill M, Jacobsen E, Manni M, Civallero M, Skrypets T, Lymboussaki A, Federico M, Kim Y, Kim J, Cho J, Eipe T, Shet T, Epari S, Shetty A, Saha S, Jain H, Sengar M, Van Der Weyden C, Prince H, Hamouche R, Muradashvili T, Foss F, Gentilini M, Casadei B, Zinzani P, Okatani T, Yoshida N, Yoon S, Kim W, Panchoo G, Mohamed Z, Verburgh E, Alturas J, Al-Mansour M, Ford J, Cabrera M, Ku A, Bhagat G, Ma H, Sawas A, Kariya K, Iwasaki M, Bhanushali F, O'Connor O, Marchi E, Shen C, Shah D, Jain S. Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: Results from PETAL consortium. Blood Advances 2024 PMID: 39481087, DOI: 10.1182/bloodadvances.2024014674.Peer-Reviewed Original ResearchNK-cell lymphomasOverall survivalMature T cellsALK-ALCLNK cellsT cellsAssociated with 3-year OSTiming of second-line treatmentSuperior median overall survivalMedian overall survivalPrimary refractory diseaseProgression-free survivalInternational retrospective cohort studySecond-line treatmentEfficacy of novel drugsIdentified several independent predictorsRetrospective cohort studyR/R lymphomaExtranodal sitesPTCL-NOSIntermediate-riskCytotoxic chemotherapyHistological subtypesRefractory diseaseRelapsed lymphomaReal World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma
Straining R, Foss F, Schiffer M, Amin K, Agarwal S, Isufi I, Huntington S, Kothari S, Seropian S, Girardi M, Sethi T. Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2024 PMID: 39368885, DOI: 10.1016/j.clml.2024.09.005.Peer-Reviewed Original ResearchT-cell lymphomaHeterogeneous group of lymphoid malignanciesGroup of lymphoid malignanciesPeripheral T-cell lymphomaAggressive T-cell lymphomaCutaneous T-cell lymphomaT cellsResponse rateR/R settingComplete responseLymphoid malignanciesPoor outcomeAnaplastic large cell lymphomaFrontline treatment regimensLarge cell lymphomaCombination of prednisoneHeterogeneous groupCell lymphomaChemotherapy optionsCaucasian patientsFirst-linePositive patientsTreatment regimensGrade 3LymphomaClinical and Histologic Variants of CD8+ Cutaneous T-Cell Lymphomas
Swallow M, Micevic G, Zhou A, Carlson K, Foss F, Girardi M. Clinical and Histologic Variants of CD8+ Cutaneous T-Cell Lymphomas. Cancers 2024, 16: 3087. PMID: 39272944, PMCID: PMC11394026, DOI: 10.3390/cancers16173087.Peer-Reviewed Original ResearchT-cell lymphomaPrimary cutaneous gamma/delta T-cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaLymphoproliferative disordersMycosis fungoidesCD8+ cutaneous T-cell lymphomasCutaneous gamma/delta T-cell lymphomaPanniculitis-like T-cell lymphomaGamma/delta T-cell lymphomaCytotoxic T-cell lymphomaT-cell lymphoproliferative disorderAbnormal T-cell populationCutaneous T-cell lymphomaCytotoxic molecule expressionT cell populationsIndicator of prognosisAppropriate treatment planCD8-positiveAggressive entityLymphomatoid papulosisHistological variantsHistopathological differentiationTreatment algorithmCD8Clinical manifestationsValemetostat Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphomas: Primary Results From a Phase 1 Trial
Maruyama D, Porcu P, Tobinai K, Allen P, Ishitsuka K, Tsukasaki K, Kusumoto S, Narita T, Foss F, Yamauchi N, Yuda J, Morishima S, Imaizumi Y, Izutsu K, Feldman T, Kawamata T, Kakurai Y, Yamauchi H, Biserna N, Inoue A, Tachibana M, Hizukuri Y, Horwitz S, Jacobsen E. Valemetostat Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphomas: Primary Results From a Phase 1 Trial. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s229. DOI: 10.1016/s2152-2650(24)00908-x.Peer-Reviewed Original ResearchTCL-391 Valemetostat Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphomas: Primary Results From a Phase 1 Trial
Maruyama D, Porcu P, Tobinai K, Allen P, Ishitsuka K, Tsukasaki K, Kusumoto S, Narita T, Foss F, Yamauchi N, Yuda J, Morishima S, Imaizumi Y, Izutsu K, Feldman T, Kawamata T, Kakurai Y, Yamauchi H, Biserna N, Maruyama A, Tachibana M, Hizukuri Y, Horwitz S, Jacobsen E. TCL-391 Valemetostat Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphomas: Primary Results From a Phase 1 Trial. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s523-s524. DOI: 10.1016/s2152-2650(24)01617-3.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsB-NHLR/R NHLPartial responseEZH2 mutationsAdverse eventsMedian duration of responseRecommended phase 2 doseRelapsed/refractory non-Hodgkin lymphomaTreatment-related adverse eventsPhase 2 doseR/R follicular lymphomaNon-Hodgkin's lymphomaDuration of responseMaximum tolerated doseDecreased platelet countPhase 1 trialYears of ageFollicular lymphomaTolerated doseDose reductionOpen-labelMedian durationEfficacy analysisMedian ageP-088 Evaluating T-cell Fitness Pre B-Cell Maturation Antigen (BCMA)-Targeted T-Cell Redirection Therapies (TRT) as a Predictive Marker for Efficacy/Toxicity in Relapsed/Refractory Multiple Myeloma (RRMM)
Theprungsirikul P, Yu M, Liu Y, Rall K, Matthews M, Neparidze N, Parker T, Browning S, Anderson T, Stevens E, Foss F, Gowda L, Pillai M, Isufi I, Seropian S, Mirza S, Bar N. P-088 Evaluating T-cell Fitness Pre B-Cell Maturation Antigen (BCMA)-Targeted T-Cell Redirection Therapies (TRT) as a Predictive Marker for Efficacy/Toxicity in Relapsed/Refractory Multiple Myeloma (RRMM). Clinical Lymphoma Myeloma & Leukemia 2024, 24: s92-s93. DOI: 10.1016/s2152-2650(24)01991-8.Peer-Reviewed Original ResearchPhase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma
Witzig T, Sokol L, Kim W, de la Cruz Vicente F, García-Sancho A, Advani R, Vidal J, de Oña Navarrete R, Marin-Niebla A, Izquierdo A, Terol M, Domingo-Domenech E, Saunders A, Bendris N, Mackey J, Leoni M, Foss F. Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma. Blood Advances 2024, 8: 4581-4592. PMID: 38991123, PMCID: PMC11401221, DOI: 10.1182/bloodadvances.2024012806.Peer-Reviewed Original ResearchRelapsed/refractory peripheral T-cell lymphomaAngioimmunoblastic T-cell lymphomaPeripheral T-cell lymphomaT-cell lymphomaProgression-free survivalDuration of responseAdverse eventsAngioimmunoblastic T-cell lymphoma patientsMedian duration of responseMedian progression-free survivalSafety of tipifarnibHematologic adverse eventsMedian overall survivalTreatment-related deathsBiomarkers of responsePhase 2 trialSixty-five patientsFarnesyltransferase inhibitor tipifarnibNon-responder groupTumor mutational profileSingle-arm trialPTCL-NOSOpen-labelOverall survivalPrimary endpoint572 Development of immunotherapies targeting TCR-Vβ2 for treatment of cutaneous T cell lymphoma
Ren J, Liao X, Lewis J, Li D, Chang J, Swallow M, Lee J, Qu R, Carlson K, Foss F, Girardi M. 572 Development of immunotherapies targeting TCR-Vβ2 for treatment of cutaneous T cell lymphoma. Journal Of Investigative Dermatology 2024, 144: s100. DOI: 10.1016/j.jid.2024.06.588.Peer-Reviewed Original ResearchCosts of care during chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell lymphomas
Di M, Potnis K, Long J, Isufi I, Foss F, Seropian S, Gross C, Huntington S. Costs of care during chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell lymphomas. JNCI Cancer Spectrum 2024, 8: pkae059. PMID: 39115391, PMCID: PMC11340641, DOI: 10.1093/jncics/pkae059.Peer-Reviewed Original ResearchChimeric antigen receptor T-cell therapyB-cell lymphomaRelapsed/refractory B-cell lymphomaT-cell therapyCAR-T administrationCAR-T productsMedian total costCommercially insured patientsReal-world costsMedian costOut-of-pocket copaymentsCost of careLymphomaMonthly costTherapyPatientsProduct acquisitionFinancial outcomesHigher upfront costChart review study of real-world clinical outcomes in patients with cutaneous T-cell lymphoma treated with extracorporeal photopheresis in the US in 2017–2019
Girardi M, Carlson K, Huang X, Corman S, Edmundson P, Schmier J, Kale H, Raina R, Foss F. Chart review study of real-world clinical outcomes in patients with cutaneous T-cell lymphoma treated with extracorporeal photopheresis in the US in 2017–2019. Journal Of Dermatological Treatment 2024, 35: 2360568. PMID: 38852942, DOI: 10.1080/09546634.2024.2360568.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaCutaneous T-cell lymphoma patientsExtracorporeal photopheresisResponse rateClinical outcomesMonths of ECP treatmentMedian time to responseReal-world treatment patternsECP initiationLymph node involvementStage IV diseaseAdvanced-stage diseaseT-cell lymphomaTime to responseEffective treatment optionPercentage of patientsChart review studyIV diseaseSezary syndromeNode involvementConcomitant therapySystemic therapyMedian ageMycosis fungoidesChart reviewAssociations of T-cell fitness prior to B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor T-cell (CART) and bispecific T-cell engager (BiTE) therapies and efficacy/toxicity in relapsed/refractory multiple myeloma (RRMM).
Theprungsirikul P, Yu M, Rall K, Matthews M, Neparidze N, Parker T, Browning S, Anderson T, Stevens E, Foss F, Gowda L, Pillai M, Isufi I, Seropian S, Mirza S, Bar N. Associations of T-cell fitness prior to B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor T-cell (CART) and bispecific T-cell engager (BiTE) therapies and efficacy/toxicity in relapsed/refractory multiple myeloma (RRMM). Journal Of Clinical Oncology 2024, 42: 7549-7549. DOI: 10.1200/jco.2024.42.16_suppl.7549.Peer-Reviewed Original ResearchChimeric antigen receptor T cellsRelapsed/refractory multiple myelomaT cell fitnessHigh-risk cytogeneticsCytokine release syndromeNon-respondersExtramedullary diseaseT cellsPeripheral blood prior to treatmentInternational Myeloma Working Group criteriaNR groupBlood prior to treatmentBispecific T-cell engagerMedian follow-up timeMedian prior linesT-cell therapyPost-treatment follow-upT-cell engagersT cell influxT-cell %Working Group criteriaYale Cancer CenterMann-Whitney U testResponse to disease progressionIdecabtagene vicleucelAllogeneic transplantation and cellular therapies in cutaneous T-cell lymphoma
Goyal A, Foss F. Allogeneic transplantation and cellular therapies in cutaneous T-cell lymphoma. Expert Review Of Anticancer Therapy 2024, 24: 41-58. PMID: 38224371, DOI: 10.1080/14737140.2024.2305356.Peer-Reviewed Original ResearchConceptsDonor lymphocyte infusionTotal body irradiationT-cell lymphomaCAR-T cell therapyCutaneous T-cell lymphomaT-cell therapySezary syndromeAllo-HSCTT cellsLymphocyte infusionCAR-TMycosis fungoidesAllogeneic hematopoietic stem cell transplantationCAR-T cell persistenceReduced-intensity conditioning regimensHematopoietic stem cell transplantationAdvanced stage MFTemporary disease controlTreatment of MF/SSCAR-T therapyInduce complete remissionCurative treatment optionStem cell transplantationNonmalignant T cellsTime of transplantationGeneration and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy
Ren J, Liao X, Lewis J, Chang J, Qu R, Carlson K, Foss F, Girardi M. Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy. Nature Communications 2024, 15: 519. PMID: 38225288, PMCID: PMC10789731, DOI: 10.1038/s41467-024-44786-2.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityDonor T cellsT cellsAdeno-associated virus transductionHealthy donor T cellsHost-versus-graft reactivityEnhanced antibody-dependent cellular cytotoxicityCAR-T cellsGraft-versus-hostT cell killingT-cell malignanciesMalignant T cellsNormal T-cellT cell receptorOff-target toxicityPre-existing immunoreactivityCAR-TDisease relapseCellular cytotoxicityVirus transductionCurrent treatmentPersister killingFc engineeringB2MIn vivo
2023
CAR T-Related Toxicities Based on Dynamic Proteomic Profiles Identifies Risk Factors for Cytokine Release Syndrome (CRS) and Immune Effector Cell -Associated Neurotoxicity Syndrome (ICANS)
Kewan T, Mirza S, Pine A, Rasheed Y, Hamouche R, Leveille E, Goshua G, Gu S, Liu Y, Vanoudenhove J, Bar N, Neparidze N, Foss F, Gowda L, Isufi I, Halene S, Lee A, Seropian S. CAR T-Related Toxicities Based on Dynamic Proteomic Profiles Identifies Risk Factors for Cytokine Release Syndrome (CRS) and Immune Effector Cell -Associated Neurotoxicity Syndrome (ICANS). Blood 2023, 142: 2132. DOI: 10.1182/blood-2023-187295.Peer-Reviewed Original ResearchCytokine release syndromeDiffuse large B-cell lymphomaCAR T-cell therapyCAR T-cell productsCAR-T productsNon-Hodgkin lymphomaBest cutoff pointMultiple myelomaHigher oddsDay 3Risk factorsTime pointsCutoff pointDay 5Day 0Median absolute lymphocyte countChimeric antigen receptor T cellsRefractory non-Hodgkin lymphomaCAR T-cell infusionAntigen receptor T cellsLarge B-cell lymphomaCAR-T activationFludarabine/cyclophosphamideHigher baseline CRPPossible inflammatory mediatorsNovel Causal Inference Method Estimates Treatment Effects of Contemporary Drugs in a Global Cohort of Patients with Relapsed and Refractory Mature T-Cell and NK-Cell Neoplasms
Koh M, Boussi L, Han J, Peng L, Sorial M, Eche-Ugwu I, Miranda E, Chiattone C, Stuver R, Horwitz S, Turizo M, McCabe S, Merrill M, Jacobsen E, Kim J, Kim Y, Cho J, Eipe T, Shet T, Jain H, Sengar M, Singh S, Gabler J, Koh M, Van Der Weyden C, Prince M, Hamouche R, Muradashvili T, Foss F, Gentilini M, Casadei B, Zinzani P, Okatani T, Yoshida N, Yoon S, Kim W, Panchoo G, Mohamed Z, Verburgh E, Alturas J, Al Mansour M, Ford J, Manni M, Federico M, O'Connor O, Cabrera M, Shen C, Marchi E, Shah D, Jain S. Novel Causal Inference Method Estimates Treatment Effects of Contemporary Drugs in a Global Cohort of Patients with Relapsed and Refractory Mature T-Cell and NK-Cell Neoplasms. Blood 2023, 142: 1703. DOI: 10.1182/blood-2023-185881.Peer-Reviewed Original ResearchSuperior overall survivalCytotoxic chemotherapyOverall survivalNK-cell neoplasmsBrentuximab vedotinPTCL-NOSMultivariate CoxSingle agentALK- ALCLSmall molecule inhibitorsComparable OSGlobal cohortLargest global cohortClinical trialsT cellsConcordance indexMultivariate Cox regression modelSecond-line therapyPrimary refractory patientsIndependent prognostic effectCox regression modelMolecule inhibitorsReal-world evidenceEpigenetic modifiersMature T cellsValemetostat for Relapsed or Refractory Peripheral T-Cell Lymphomas: Primary Results from a Phase 1 Trial
Jacobsen E, Maruyama D, Porcu P, Tobinai K, Allen P, Ishitsuka K, Tsukasaki K, Kusumoto S, Foss F, Yamauchi N, Morishima S, Imaizumi Y, Izutsu K, Feldman T, Kawamata T, Kakurai Y, Yamauchi H, Biserna N, Inoue A, Tsutsumi S, Horwitz S. Valemetostat for Relapsed or Refractory Peripheral T-Cell Lymphomas: Primary Results from a Phase 1 Trial. Blood 2023, 142: 303. DOI: 10.1182/blood-2023-172512.Peer-Reviewed Original ResearchPeripheral T-cell lymphomaAdult T-cell leukemia/lymphomaT-cell non-Hodgkin lymphomaObjective response rateDuration of responseProgression-free survivalT-cell lymphomaMedian DORATLL groupPTCL groupData cutoffAdverse eventsClinical activityResponse rateRefractory peripheral T-cell lymphomaMedian progression-free survivalAngioimmunoblastic T-cell lymphomaT-cell leukemia/lymphomaDose-expansion cohortsDose-expansion phaseMedian prior therapiesPreliminary efficacy assessmentComplete response rateDose-escalation phasePhase 2 trialImpact of Therapy Sequence on Survival Outcomes Among Patients with Relapsed or Refractory Mature T and NK Cell Neoplasms: A Global Retrospective Cohort Study
Sorial M, Koh M, Boussi L, Han J, Peng L, Eche-Ugwu I, Duan R, Lei M, Miranda E, Chiattone C, Stuver R, Horwitz S, Turizo M, McCabe S, Merrill M, Jacobsen E, Kim J, Kim Y, Cho J, Jain H, Sengar M, Eipe T, Shet T, Singh S, Lou U, Raghib H, Gabler J, Koh M, Van Der Weyden C, Prince M, Hamouche R, Muradashvili T, Foss F, Gentilini M, Casadei B, Zinzani P, Okatani T, Yoshida N, Yoon S, Kim W, Panchoo G, Mohamed Z, Verburgh E, Alturas J, Al Mansour M, Ford J, Manni M, Federico M, O'Connor O, Cabrera M, Marchi E, Shen C, Shah D, Jain S. Impact of Therapy Sequence on Survival Outcomes Among Patients with Relapsed or Refractory Mature T and NK Cell Neoplasms: A Global Retrospective Cohort Study. Blood 2023, 142: 3080. DOI: 10.1182/blood-2023-182341.Peer-Reviewed Original ResearchNK-cell neoplasmsTherapy sequenceCohort studyMost patientsSurvival outcomesPatient cohortCox modelAnaplastic large cell lymphomaFirst lineAllogeneic hematopoietic transplantOptimal therapy sequencePTCL-NOS patientsRetrospective cohort studyKaplan-Meier curvesLarge cell lymphomaEpigenetic modifiersImmunomodulatory imide drugsPI3K inhibitorsAntibody-drug conjugatesAllogeneic HSCTCommon histologyPlanned subgroupPrimary refractoryAutologous HSCTHazard ratioAllogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis
Goyal A, O’Leary D, Foss F. Allogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis. Bone Marrow Transplantation 2023, 59: 41-51. PMID: 37853164, DOI: 10.1038/s41409-023-02122-0.Peer-Reviewed Original ResearchConceptsGraft-versus-host diseaseReduced-intensity conditioningDonor lymphocyte infusionAllo-HSCTStem cell transplantationMyeloablative conditioningSezary syndromeOverall survivalMycosis fungoidesCell transplantationRates of graft-versus-host diseaseTreated with donor lymphocyte infusionsChronic graft-versus-host diseaseAllogeneic hematopoietic stem cell transplantationMeta-analysisAdvanced-stage mycosis fungoidesAssociated with superior OSGraft-versus-lymphoma effectOutcomes of allo-HSCTAllogeneic stem cell transplantationHematopoietic stem cell transplantationTreatment of mycosis fungoidesGraft-versus-lymphomaNon-relapse mortalityProgression-free survivalCost-effectiveness of chimeric antigen receptor T-cell therapy in adults with relapsed or refractory follicular lymphoma
Potnis K, Di M, Isufi I, Gowda L, Seropian S, Foss F, Forman H, Huntington S. Cost-effectiveness of chimeric antigen receptor T-cell therapy in adults with relapsed or refractory follicular lymphoma. Blood Advances 2023, 7: 801-810. PMID: 36342852, PMCID: PMC10011202, DOI: 10.1182/bloodadvances.2022008097.Peer-Reviewed Original ResearchConceptsCAR T-cell therapyT-cell therapyQuality-adjusted life yearsIncremental cost-effectiveness ratioCAR T cellsChimeric antigen receptor T-cell therapySOC therapyFollicular lymphomaT cellsLife yearsR FLRefractory follicular lymphomaT cell strategiesThird-line settingLines of therapyIncremental clinical benefitUS payer perspectiveCost-effectiveness ratioTherapy remissionUnselected patientsCare therapyClinical benefitClinical trialsTreatment strategiesPayer perspective