The treatment landscape for multiple myeloma (MM) has rapidly evolved over the last 2 decades. The development of triplet and quadruplet regimens including proteasome inhibitors (PI), immunomodulatory agents (IMiDs), and anti-CD38 monoclonal antibodies has dramatically extended overall survival. In addition to effective multidrug regimens, autologous stem cell transplant (ASCT) is a cornerstone of management in newly diagnosed multiple myeloma (NDMM). However, despite these combined treatment modalities, curative therapy for MM remains elusive. Recent, novel immunotherapies including chimeric antigen T-cell (CAR-T) therapy have demonstrated deep and durable responses in relapsed and refractory multiple myeloma (RRMM). Currently 2 CAR-T products, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), are approved by the FDA for the treatment of RRMM. The success of CAR-T therapy revolutionized the management of RRMM prompting clinical trials studying CAR-T therapy in the first line setting. The ongoing KarMMa-4, CARTITUDE-5, and CARTITUDE-6 clinical trials may establish CAR-T therapy as a first line option potentially supplanting ASCT in the initial treatment of NDMM. In this review, we discuss the current standard of care management of NDMM, trace the evolution of CAR-T clinical trials in RRMM, and survey ongoing clinical trials studying CAR-T therapy in NDMM.
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http://dx.doi.org/10.1016/j.clml.2024.01.001 | DOI Listing |
Background: FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.
View Article and Find Full Text PDFAdv Mater
January 2025
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, China.
Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety of cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation-from the chemical composition and physical properties to the precision control of nanoassemblies.
View Article and Find Full Text PDFMol Ther
January 2025
Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China; Shenzhen University-Haoshi Cell Therapy Institute, Shenzhen, China. Electronic address:
Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Claudin18.2 is highly expressed in PC tissue and could serve as a suitable target for CAR-T therapy.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
The treatment of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-cell ALL) has seen substantial progress over the past two decades. The introduction of tyrosine kinase inhibitor (TKIs) has resulted in dramatic improvements in long-term survival. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), with its curative potential, has always been an integral part of the treatment algorithm of Ph+ ALL.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy.
Background/objectives: Hematopoietic cell transplantation (HCT) is a curative treatment for various hematological diseases but can lead to complications which increase malnutrition risk, particularly in allogeneic transplantation patients. This study evaluates the nutritional status evolution of patients undergoing HCT during hospitalization and follow-up.
Methods: This retrospective observational study included 365 patients, divided into two groups: 134 underwent allogeneic HCT, while 231 underwent autologous transplantation or CAR-T therapy.
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