The rapid emergence of CD20-targeting T-cell engagers in follicular lymphoma and large B-cell lymphoma has further expanded the treatment options for patients with relapsed or refractory disease. Herein, we review and discuss the standard-of-care products and indications for mosunetuzumab, epcoritamab, and glofitamab. We provide a detailed overview of the registrational clinical trials, as well as a review of ongoing trials and likely future indications. We also address how we incorporate T-cell engagers in our current treatment paradigm, with particular emphasis on their use with and as alternatives to chimeric antigen receptor T-cell therapy. We further discuss our management of immune effector cell-related toxicities.
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Blood Adv
January 2025
City of Hope Medical Center, Duarte, California, United States.
Despite the success of the CD19xCD3 T cell engager blinatumomab in B-cell acute lymphoblastic leukemia (B-ALL), treatment failure is common and can manifest with antigen loss and extramedullary disease (EMD) relapse. To understand the impact of leukemia genetics on outcomes, we reviewed 267 adult patients with B-ALL treated with blinatumomab and used next generation sequencing to identify molecular alterations. Patients received blinatumomab for relapsed/refractory (R/R) disease (n=150), minimal residual disease (MRD+) (n=88), upfront as induction (n=10), or as consolidation in MRD- state (n=19).
View Article and Find Full Text PDFClin Adv Hematol Oncol
December 2024
Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, Kansas.
The rapid emergence of CD20-targeting T-cell engagers in follicular lymphoma and large B-cell lymphoma has further expanded the treatment options for patients with relapsed or refractory disease. Herein, we review and discuss the standard-of-care products and indications for mosunetuzumab, epcoritamab, and glofitamab. We provide a detailed overview of the registrational clinical trials, as well as a review of ongoing trials and likely future indications.
View Article and Find Full Text PDFBlood Rev
January 2025
Department of Hematology, First Hospital of Jilin University, Changchun, Jilin, China. Electronic address:
Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined.
View Article and Find Full Text PDFNat Rev Rheumatol
January 2025
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
B cell depletion with rituximab, a chimeric monoclonal antibody that selectively targets B cells by binding CD20, has been used off label in severe and resistant systemic lupus erythematosus (SLE) for over two decades. Several biological mechanisms limit the efficacy of rituximab, including immunological reactions towards the chimeric molecule, increased numbers of residual B cells, including plasmablasts and plasma cells, and a post-treatment surge in B cell-activating factor (BAFF) levels. Consequently, rituximab induces remission in only a proportion of patients, and safety issues limit its use.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Certara Predictive Technologies Division, Certara UK Limited, Sheffield, UK.
Understanding cytokine-related therapeutic protein-drug interactions (TP-DI) is crucial for effective medication management in conditions characterized by elevated inflammatory responses. Recent FDA and ICH guidelines highlight a systematic, risk-based approach for evaluating these interactions, emphasizing the need for a thorough mechanistic understanding of TP-DIs. This study integrates the physiologically based pharmacokinetic (PBPK) model for TP (specifically interleukin-6, IL-6) with small-molecule drug PBPK models to elucidate cytokine-related TP-DI mechanistically.
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