Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
Sattva S. Neelapu,Frederick L. Locke,Nancy L. Bartlett,Lazaros J. Lekakis,David B. Miklos,Caron A. Jacobson,Ira Braunschweig,Olalekan O. Oluwole,Tanya Siddiqi,Yi Lin,John M. Timmerman,Patrick J. Stiff,Jonathan W. Friedberg,Ian W. Flinn,Andre Goy,Brian T. Hill,Mitchell R. Smith,Abhinav Deol,Umar Farooq,Peter A. McSweeney,Javier Munoz,Irit Avivi,Januario E. Castro,Jason R. Westin,Julio C. Chavez,Armin Ghobadi,Krishna V. Komanduri,Ronald Levy,Eric D. Jacobsen,Thomas E. Witzig,Patrick M. Reagan,Adrian Bot,John J. Rossi,Lynn Navale,Yizhou Jiang,Jeff Aycock,Meg Elias,David Z. Chang,Jeff Wiezorek,William Y. Go +39 more
TLDR
Patients with refractory large B‐cell lymphoma who received CAR T‐cell therapy with axi‐cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events.Abstract:
BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%)....read more
Citations
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Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma
Giulia Agliardi,Anna Rita Liuzzi,Alastair Hotblack,Donatella De Feo,Nicolás Gonzalo Núñez,Cassandra L Stowe,Ekaterina Friebel,Francesco Nannini,Lukas Rindlisbacher,Thomas A. Roberts,Rajiv Ramasawmy,Iwan P. Williams,Bernard Siow,Bernard Siow,Mark F. Lythgoe,Tammy L. Kalber,Sergio A. Quezada,Martin Pule,Sonia Tugues,Karin Straathof,Karin Straathof,Burkhard Becher +21 more
TL;DR: This article showed that IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4+ T cells, decreased numbers of regulatory T cells and activation of the myeloid compartment.
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Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma.
Jennifer M. Logue,Elisa Zucchetti,Christina A Bachmeier,Gabriel S Krivenko,Victoria Larson,Daniel Ninh,Giovanni Grillo,Biwei Cao,Jongphil Kim,Julio C. Chavez,Aliyah Baluch,Farhad Khimani,Aleksandr Lazaryan,Taiga Nishihori,Hien D. Liu,Javier Pinilla-Ibarz,Bijal D. Shah,Rawan Faramand,Anna E. Coghill,Marco L. Davila,Bhagirathbhai Dholaria,Michael D. Jain,Frederick L. Locke +22 more
TL;DR: Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time, but most patients experience profound and prolonged CD4 T-cell immunosuppression without severe infection.
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In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma.
Matthew J. Frank,Patrick M. Reagan,Nancy L. Bartlett,Leo I. Gordon,Jonathan W. Friedberg,Debra K. Czerwinski,Steven R. Long,Richard T. Hoppe,Robert Janssen,Albert Candia,Robert L. Coffman,Ronald Levy +11 more
TL;DR: In situ vaccination with the TLR9 agonist SD-101, along with low-dose radiation, was safe and induced systemic responses in patients with indolent lymphoma and predicted favorable response to treatment.
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Double hit and double expressors in lymphoma: Definition and treatment
Peter A. Riedell,Sonali M. Smith +1 more
TL;DR: Double‐expressor lymphoma (DEL), defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, is not a distinct entity in the current World Health Organization classification but accounts for 20% to 30% of DLBCL cases and also has poor outcomes.
Journal ArticleDOI
Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy
Tania Jain,Tania Jain,Merav Bar,Ankit Kansagra,Elise A. Chong,Shahrukh K. Hashmi,Shahrukh K. Hashmi,Sattva S. Neelapu,Michael Byrne,Elad Jacoby,Aleksandr Lazaryan,Caron A. Jacobson,Stephen M. Ansell,Farrukh T. Awan,Linda J. Burns,Veronika Bachanova,Catherine M. Bollard,Paul A. Carpenter,John F. DiPersio,Mehdi Hamadani,Helen E. Heslop,Joshua A. Hill,Joshua A. Hill,Krishna V. Komanduri,Craig Kovitz,Hillard M. Lazarus,Justin M. Serrette,Mohamad Mohty,David B. Miklos,Arnon Nagler,Steven Z. Pavletic,Bipin N. Savani,Stephen J. Schuster,Mohamed A. Kharfan-Dabaja,Miguel-Angel Perales,Miguel-Angel Perales,Yi Lin +36 more
TL;DR: Advice is provided from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the utilization of CD19 CAR T for the treatment of NHL.
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TL;DR: Diagnostic criteria for a severe cytokine release syndrome (sCRS) is defined and serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS.
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