2024
Predictors of response to venetoclax and therapeutic potential of CDK7 inhibition in multiple myeloma
Dutta R, Thibaud S, Leshchenko V, Ram M, Melnekoff D, Bhalla S, Restrepo P, Gupta V, Barwick B, Newman S, McCafferty J, Hantash F, Nooka A, Cho H, Richard S, Rodriguez C, Rossi A, Sanchez L, Chari A, Boise L, Jagannath S, Richter J, Parekh S, Laganà A. Predictors of response to venetoclax and therapeutic potential of CDK7 inhibition in multiple myeloma. Blood Neoplasia 2024, 1: 100049. DOI: 10.1016/j.bneo.2024.100049.Peer-Reviewed Original ResearchCyclin-dependent kinase 7Progression-free survivalMultiple myelomaAnalysis of RNA-seq dataMM cellsTherapeutic strategiesPatients treated with venetoclaxCDK7 inhibitor THZ1Overcome venetoclax resistanceRNA-seq dataSix-gene signaturePredictors of responseChromosome 1q gainPersonalized therapeutic strategiesDevelopment of personalized therapeutic strategiesInduce cell deathMarkers of sensitivityBCL2 inhibitorsCDK7 inhibitionMCL1 genePrognostic importanceStratify patientsCyclin-dependentMCL1 levelsPatient populationA Randomized Trial Demonstrates a 3-Shot Flu Vaccine Series Improves Protection over a Single Shot in Multiple Myeloma
Hofmeister C, Gupta V, Kaufman J, Nooka A, Joseph N, Lonial S, Dhodapkar M. A Randomized Trial Demonstrates a 3-Shot Flu Vaccine Series Improves Protection over a Single Shot in Multiple Myeloma. Blood 2024, 144: 255-255. DOI: 10.1182/blood-2024-202102.Peer-Reviewed Original ResearchPlasma cell disorderStandard armInfluenza vaccineMyeloma patientsIntensive armDaratumumab exposureRandomized controlled trialsMultiple myelomaFlu seasonCell disordersHistory of severe allergic reactionsStandard-dose influenza vaccinesTreat analysisRisk of influenza-like illnessT-cell engagersSeasonal influenza vaccineHigh dose vaccineHigh dose injectionsInfluenza-like illnessProportion of patientsFlu vaccinationVaccine preventable illnessYears of ageSevere allergic reactionsStatistically significant differenceGenomic Determinants of Clinical Outcomes in Multiple Myeloma with t(11;14)(CCND1;IGH) Treated with Venetoclax
Kaddoura M, Wiedmeier-Nutor J, Gupta V, Ziccheddu B, Shivaram S, Tang H, Fonseca R, Durante M, Matulis S, Jelinek T, Landgren O, Mitsiades C, Bergsagel P, Braggio E, Boise L, Fonseca R, Kumar S, Maura F, Baughn L. Genomic Determinants of Clinical Outcomes in Multiple Myeloma with t(11;14)(CCND1;IGH) Treated with Venetoclax. Blood 2024, 144: 249. DOI: 10.1182/blood-2024-204071.Peer-Reviewed Original ResearchProgression free survivalSingle nucleotide variantsWhole-genome sequencingMultiple myelomaMM patientsFocal deletionsCopy number variantsMechanisms of resistanceTraining cohortValidation cohortChronic lymphocytic leukemia treated with venetoclaxDisease progressionMAPK pathwayMedian progression free survivalPopulation of MM patientsDeterminants of clinical outcomeAnti-CD38 agentsTreated with venetoclaxComprehensive genomic profilingMAPK pathway mutationsStructural variantsAcute myeloid leukemiaGenomic eventsLoss of NoxaNovel drug combinationsThe Role of NOXA in Venetoclax Treatment Response in Multiple Myeloma
Shivaram S, Yan H, Tang H, Anderson H, Kaddoura M, Wiedmeier-Nutor J, Tian S, Howe M, Bolarinwa A, Zepeda Mendoza C, Gupta V, Lehman S, Mitsiades C, Bergsagel P, Braggio E, Boise L, Fonseca R, Maura F, Kumar S, Baughn L. The Role of NOXA in Venetoclax Treatment Response in Multiple Myeloma. Blood 2024, 144: 4635-4635. DOI: 10.1182/blood-2024-205385.Peer-Reviewed Original ResearchMayo Clinic cohortNoxa proteinMultiple myelomaG alleleIncreased expressionGene expressionCyclin D1Clinical cohortExpression of CCND1Cell linesAllele specific effectsBCL-2 inhibitor venetoclaxLevels of NoxaHistone mark H3K27acG risk allelePrimary cytogenetic abnormalityPlasma cell malignancyAssociated with increased expressionRNA sequencing dataHuman myeloma cell linesKO cell linesWestern blottingAnalyzed whole-exomeChIP-seqWhole genomeIberdomide Alone or in Combination with Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma (SMM)
Joseph N, Kaufman J, Hofmeister C, Gupta V, Burton B, Pruitt R, Nooka A, Dhodapkar M, Lonial S. Iberdomide Alone or in Combination with Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma (SMM). Blood 2024, 144: 1983-1983. DOI: 10.1182/blood-2024-210335.Peer-Reviewed Original ResearchSafety run-inProgression free survivalHigh-risk smoldering myelomaSmoldering multiple myelomaSmoldering myelomaMultiple myelomaRun-inHigh-risk smoldering multiple myelomaRisk of progression to myelomaNo dose limiting toxicitiesRate of tumor regressionProgression to myelomaRecurrent grade 3Treatment of intermediate-Grade 3 thrombocytopeniaCycles of therapyDose-limiting toxicityMedian patient ageOverall survival benefitStem cell collectionToxic therapeutic optionsRisk stratification modelTreatment of intermediateRelapsed myelomaCryptococcal meningitisMitochondrial Priming Is Heterogenous in t(4;14) Multiple Myeloma and Can be Induced By Inhibition of NSD2
Matulis S, Chavez R, Owens R, Wiita A, Shanmugam M, De Matos Simoes R, Mitsiades C, Joseph N, Hofmeister C, Kaufman J, Dhodapkar M, Lonial S, Nooka A, Gupta V, Licht J, Barwick B, Boise L. Mitochondrial Priming Is Heterogenous in t(4;14) Multiple Myeloma and Can be Induced By Inhibition of NSD2. Blood 2024, 144: 4663-4663. DOI: 10.1182/blood-2024-210441.Peer-Reviewed Original ResearchDynamic BH3 profilingSensitivity to venetoclaxBH3 profilingCyto c releaseT(4;14) MMMultiple myelomaBCL2 family membersVenetoclax sensitivityBroad-spectrum peptideMitochondrial primingC releaseTKO cellsPatient samplesTreatment of multiple myelomaResistance to venetoclaxResponse to venetoclaxPredicting clinical responseT(4;14) multiple myelomaPlasma cell biologyMM cell linesAnnexin V/propidium iodide stainingHigh-risk formsDays of treatmentPrecision medicine approachBCL2 inhibitionP-342 Impact of Achieving <VGPR With Dara-RVD Induction Therapy in Newly Diagnosed Multiple Myeloma (NDMM) Patients
Joseph N, Pruitt R, Gupta V, Hofmeister C, Dhodapkar M, Nooka A, Lonial S, Kaufman J. P-342 Impact of AchievingDOI: 10.1016/s2152-2650(24)02244-4. Peer-Reviewed Original ResearchP-234 Autocrine IL6 Signaling in Stromal Cells in Multiple Myeloma Influences the Bone Marrow Microenvironment
Matulis S, Barwick B, Bombin S, Ackley J, Gupta V, Hill G, Green D, Riddell S, Lonial S, Dhodapkar M, Boise L. P-234 Autocrine IL6 Signaling in Stromal Cells in Multiple Myeloma Influences the Bone Marrow Microenvironment. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s173. DOI: 10.1016/s2152-2650(24)02137-2.Peer-Reviewed Original Research
2023
Machine Learning Models Predict Molecular Genetic Subtypes of Multiple Myeloma from Whole-Slide Bone Marrow Aspirate Smears
Lewis J, Shebelut C, Attieh M, Horwath M, Khanna A, Al-Rusan O, Ponnatt T, Smith G, Gutman D, Gupta V, Aljudi A, Cooper L, Jaye D. Machine Learning Models Predict Molecular Genetic Subtypes of Multiple Myeloma from Whole-Slide Bone Marrow Aspirate Smears. Blood 2023, 142: 7158. DOI: 10.1182/blood-2023-190686.Peer-Reviewed Original ResearchPlasma cell neoplasmsMolecular genetic subtypesBone marrow aspirate smearsMarrow aspirate smearsCell neoplasmsPlasma cellsAspirate smearsMultiple myelomaGenetic subtypesRisk stratificationBone marrow biopsy samplesCurrent prognostic systemsRisk stratification toolCommon hematologic malignancyPlasma cell morphologyMultiple myeloma casesSpecific morphologic featuresSubset of casesRecurrent genetic abnormalitiesLow-resource settingsBiologic subtypeStratification toolAggressive diseaseScanned whole slide imagesHematologic malignancies