Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
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DOI: 10.1126/scitranslmed.3008226, 224ra25 (2014);6 Sci Transl Med et al.Marco L. DavilaAcute Lymphoblastic LeukemiaEfficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Editor's Summary
CAR T cell therapy.CRS may limit the efficacy of the CAR T cell therapy. These data support the need for further multicenter trials for corticosteroids or interleukin-6 receptor blockade to curb the CRS. This is especially important because treatment forshould allow for identification of the subset of patients who will likely require therapeutic intervention with CAR T cell therapy. They found that serum C-reactive protein (CRP) associated with the severity of CRS, whichthe authors carefully characterized cytokine release syndrome (CRS), which is a series of toxicities associated with the current standard of care. Moreover,−−patients to transition to allogeneic hematopoietic stem cell transplantation The CD19-targeting CAR T cell therapy resulted in an 88% complete response rate, which allowed most of the16 relapsed or refractory adult patients. now report the results of a phase 1 clinical trial of CAR T cells inet al.with chimeric antigen receptors (CARs). Davila median survival of less than 6 months. An emerging therapy for adult B-ALL is through T cells that target tumor cells Relapsed or refractory B acute lymphoblastic leukemia (B-ALL) in adults has a poor prognosis, with an expectedCARving Out a Niche for CAR T Cell Immunotherapy
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TherapyinBCellAcuteLymphoblasticLeukemia
MarcoL.Davila,1IsabelleRiviere,1,2,3,4XiuyanWang,4ShirleyBartido,4JaePark,1KevinCurran,5StephenS.Chung,1JolantaStefanski,4OrianaBorquez-Ojeda,4MalgorzataOlszewska,4JinrongQu,4TeresaWasielewska,4QingHe,4MitsuFink,4HimalyShinglot,4MaherYoussif,4MarkSatter,4YongzengWang,4JamesHosey,4HildaQuintanilla,1ElizabethHalton,1YvetteBernal,1DianaC.G.Bouhassira,2MariaE.Arcila,6MithatGonen,7GailJ.Roboz,8PeterMaslak,1DanDouer,1MarkG.Frattini,9SergioGiralt,1,2MichelSadelain,1,2,3*RenierBrentjens1,2,3*
Wereporton16patientswithrelapsedorrefractoryBcellacutelymphoblasticleukemia(B-ALL)thatwetreatedwithautologousTcellsexpressingthe19-28zchimericantigenreceptor(CAR)specifictotheCD19antigen.Theoverallcompleteresponseratewas88%,whichallowedustotransitionmostofthesepatientstoastandard-of-carealloge-neichematopoieticstemcelltransplant(allo-SCT).Thistherapywasaseffectiveinhigh-riskpatientswithPhiladelphiachromosome–positive(Ph+)diseaseasinthosewithrelapseddiseaseafterpreviousallo-SCT.Throughsystematic
analysisofclinicaldataandserumcytokinelevelsoverthefirst21daysafterTcellinfusion,wehavedefineddiagnosticcriteriaforaseverecytokinereleasesyndrome(sCRS),withthegoalofbetteridentifyingthesubsetofpatientswhowilllikelyrequiretherapeuticinterventionwithcorticosteroidsorinterleukin-6receptorblockadetocurbthesCRS.Additionally,wefoundthatserumC-reactiveprotein,areadilyavailablelaboratorystudy,canserveasareliableindicatorfortheseverityoftheCRS.Together,ourdataprovidestrongsupportforconductingamulticenterphase2studytofurtherevaluate19-28zCARTcellsinB-ALLandaroadmapforpatientmanagementatcentersnowcon-templatingtheuseofCARTcelltherapy.
