Browsing by Subject "CAR T-cells"

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    ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Multiple Myeloma
    (Elsevier, 2022) Dhakal, Binod; Shah, Nina; Kansagra, Ankit; Kumar, Ambuj; Lonial, Sagar; Garfall, Alfred; Cowan, Andrew; Poudyal, Bishesh Sharma; Costello, Caitlin; Gay, Francesca; Cook, Gordon; Quach, Hang; Einsele, Herman; Schriber, Jeff; Hou, Jian; Costa, Luciano; Aljurf, Mahmoud; Chaudhry, Maria; Beksac, Meral; Prince, Miles; Mohty, Mohamad; Janakiram, Murali; Callander, Natalie; Biran, Noa; Malhotra, Pankaj; Rodriguez Otero, Paula; Moreau, Philippe; Abonour, Rafat; Iftikhar, Raheel; Silberman, Rebecca; Mailankody, Sham; Gregory, Tara; Lin, Yi; Carpenter, Paul; Hamadani, Mehdi; Usmani, Saad; Kumar, Shaji; Medicine, School of Medicine
    Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.
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    CART Immunotherapy: Development, Success, and Translation to Malignant Gliomas and Other Solid Tumors
    (Frontiers Media, 2018-10-17) Filley, Anna C.; Henriquez, Mario; Dey, Mahua; Neurological Surgery, School of Medicine
    T cell chimeric antigen receptor (CAR) technology has allowed for the introduction of a high degree of tumor selectivity into adoptive cell transfer therapies. Evolution of this technology has produced a robust antitumor immunotherapeutic strategy that has resulted in dramatic outcomes in liquid cancers. CAR-expressing T-cells (CARTs) targeting CD19 and CD20 have been successfully used in the treatment of hematologic malignancies, producing sustained tumor regressions in a majority of treated patients. These encouraging results have led to a historic and unprecedented FDA approval of CTL019, Novartis' CAR T-cell therapy for the treatment of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). However, the translation of this technology to solid tumors, like malignant gliomas (MG), has thus far been unsuccessful. This review provides a timely analysis of the factors leading to the success of CART immunotherapy in the setting of hematologic malignancies, barriers limiting its success in the treatment of solid tumors, and approaches to overcome these challenges and allow the application of CART immunotherapy as a treatment modality for refractory tumors, like malignant gliomas, that are in desperate need of effective therapies.