Bispecific antibodies as bridging to BCMA CAR-T cell therapy for relapsed/refractory multiple myeloma.

Establishing a strategy for sequencing of T cell redirecting therapies for relapsed/refractory multiple myeloma (RRMM) is a pressing clinical need. We longitudinally tracked the clinical and immunological impact of bispecific T cell engaging antibodies (BsAb) as bridging therapy (BT) to subsequent BCMA-directed CAR-T cell therapies in 52 RRMM patients. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared to chemotherapy, anti-CD38 or anti-SLAMF7 antibody based regimens (46%).

Impact of Previous Allogeneic Hematopoietic Stem Cell Transplantation on Chimeric Antigen Receptor (CAR) T Cell Treatment for Relapsed/Refractory Multiple Myeloma.

Background: Anti-BCMA-directed chimeric antigen receptor (CAR) T cells are effective treatment for patients with refractory/relapsed multiple myeloma (RRMM). However, little is known about the impact of previous allogeneic hematopoietic stem cell transplantation (allo-HSCT) on lymphocyte collection for production of CAR T cells and subsequent treatment with CAR T cells.

Patients And Methods: We performed a retrospective analysis of cellular composition of lymphocyte collections, CAR T cell expansion and treatment outcomes of RRMM patients undergoing therapy with idecabtagene vicleucel (ide-cel) with and without history of allo-HSCT.

Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma.

Purpose: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T.

Patients And Methods: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133).

Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.

B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells.

CAR T cell therapy in multiple myeloma, where are we now and where are we heading for?

The introduction of chimeric antigen receptor (CAR) T cells revolutionized treatment of relapsed and refractory multiple myeloma (RRMM) in recent years. Currently, two CAR T cell products-idecabtagene vicleucel and ciltacabtagene autoleucel-are approved in the United States and the European Union to treat patients with three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Moreover, seminal phase III trials of both agents in earlier lines of therapy have been published recently.

Activation of distinct inflammatory pathways in subgroups of LR-MDS.

Aberrant innate immune signaling has been identified as a potential key driver of the complex pathophysiology of myelodysplastic neoplasms (MDS). This study of a large, clinically and genetically well-characterized cohort of treatment-naïve MDS patients confirms intrinsic activation of inflammatory pathways in general mediated by caspase-1, interleukin (IL)-1β and IL-18 in low-risk (LR)-MDS bone marrow and reveals a previously unrecognized heterogeneity of inflammation between genetically defined LR-MDS subgroups. Principal component analysis resolved two LR-MDS phenotypes with low (cluster 1) and high (cluster 2) levels of IL1B gene expression, respectively.

Compartment-specific mutational landscape of clonal hematopoiesis.

Clonal hematopoiesis (CH) is characterized by somatic mutations in blood cells of individuals without hematologic disease. While the mutational landscape of CH in peripheral blood (PB) has been well characterized, detailed analyses addressing its spatial and cellular distribution in the bone marrow (BM) compartment are sparse. We studied CH driver mutations in healthy individuals (n = 261) across different anatomical and cellular compartments.

Linking of Rasch-Scaled Tests: Consequences of Limited Item Pools and Model Misfit.

In the context of item response theory (IRT), linking the scales of two measurement points is a prerequisite to examine a change in competence over time. In educational large-scale assessments, non-identical test forms sharing a number of anchor-items are frequently scaled and linked using two- or three-parametric item response models. However, if item pools are limited and/or sample sizes are small to medium, the sparser Rasch model is a suitable alternative regarding the precision of parameter estimation.

CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease.

Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA).

Foxp3 Regulatory T Cells in Bone and Hematopoietic Homeostasis.

The bone represents surprisingly dynamic structures that are subject to constant remodeling by the concerted action of bone-forming osteoblasts and bone-resorbing osteoclasts - two cell subsets of distinct developmental origin that are key in maintaining skeletal integrity throughout life. In general, abnormal bone remodeling due to dysregulated bone resorption and formation is an early event in the manifestation of various human bone diseases, such as osteopetrosis/osteoporosis and arthritis. But bone remodeling is also closely interrelated with lympho-hematopoietic homeostasis, as the bone marrow niche is formed by solid and trabecular bone structures that provide a framework for the long-term maintenance and differentiation of HSCs (>blood lineage cells and osteoclasts) and MSCs (>osteoblasts).

SWEF Proteins Distinctly Control Maintenance and Differentiation of Hematopoietic Stem Cells.

SWAP-70 and DEF6, two proteins that feature similar domain and motif arrangements, are mainly known for their functions in differentiated hematopoietic cells. Both proteins interact with and regulate RhoGTPases and F-actin dynamics, yet their role in hematopoietic stem and precursor cells (HSPCs) remained unexplored. Here, the role of the SWEF proteins SWAP-70 and DEF6 in HSPCs was examined.

The role of the BDNF Val66Met polymorphism in individual differences in long-term memory capacity.

The protein brain-derived neurotrophic factor (BDNF) plays an important role in diverse memory processes and is strongly expressed in the hippocampus. The hippocampus itself is a key structure involved in the processing of information from short-term to long-term memory. Due to the putative role of BDNF in memory consolidation, a prominent single nucleotide polymorphism (SNP) on the BDNF gene (BDNF Val66Met) was investigated in the context of long-term memory performance.