CAR T-cell therapy to treat multiple myeloma: current state and future directions.

Chimeric antigen receptor (CAR) T-cell therapy represents a transformative advancement in treating relapsed or refractory multiple myeloma (MM) in both early- and late-line settings. MM, a plasma cell malignancy, traditionally requires ongoing complex drug regimens, posing significant burdens on patients. In contrast, CAR T-cell therapy offers a one-time treatment option without the need for continuous maintenance therapy.

Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma.

MGTA-145 or GROβT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers. Twenty-five patients with multiple myeloma enrolled in a phase 2 trial evaluating MGTA-145 and plerixafor for HSC mobilization (NCT04552743). Plerixafor was given subcutaneously followed 2 h later by MGTA-145 (0.

Clinical outcomes after idecabtagene vicleucel in older patients with multiple myeloma: a multicenter real-world experience.

The safety and efficacy of chimeric antigen receptor T-cell therapy is not well described in older patients, a population that has higher frailty and comorbidities. In this multicenter retrospective study, we evaluated clinical outcomes along with frailty and geriatric characteristics such as comorbidities, polypharmacy, falls, neuropathy, organ dysfunction, and performance status in younger (aged <65 years) vs older (aged ≥65 years) patients who received commercial idecabtagene vicleucel (ide-cel). A total of 156 patients (n = 75, aged ≥65 years) were infused with ide-cel by data cutoff.

A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia.

Although chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking.

Subthreshold micropulse laser combined with anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis.

Purpose: To evaluate the effects of subthreshold micropulse laser (SML) in addition to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME).

Methods: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were systematically searched for studies that compared anti-VEGF with SML and anti-VEGF monotherapy for DME. Outcome measures were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the number of anti-VEGF injections.

Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI.

Embracing Myeloma Chimeric Antigen Receptor-T: From Scientific Design to Clinical Impact.

Despite recent advancement of treatment strategies in multiple myeloma (MM), patients with relapsed/refractory MM disease, particularly after triple-class refractoriness, continue to have poor prognosis. Chimeric antigen receptor (CAR-T) cells were developed and applied to improve outcomes in this setting, and two products, idecabtagene vicleucel and ciltacabtagene autoleucel, both targeting B-cell maturation antigen, have been approved by the Food and Drug Administration in the United States and European Medicines Agency in Europe. Both have shown unprecedented clinical outcomes with high response rate and prolonged progression-free survival and overall survival in this patient population with grim prognosis.

Establishment of an unfed strain of and analysis of associated bacterial communities controlling its proliferation.

The ciliate harbors several hundred symbiotic algae in its cell and is widely used as an experimental model for studying symbiosis between eukaryotic cells. Currently, various types of bacteria and eukaryotic microorganisms are used as food for culturing ; thus, the cultivation conditions are not uniform among researchers. To unify cultivation conditions, we established cloned, unfed strains that can be cultured using only sterile medium without exogenous food.

Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas.

Most relapsed/refractory large B cell lymphoma (r/rLBCL) patients receiving anti-CD19 chimeric antigen receptor (CAR19) T cells relapse. To characterize determinants of resistance, we profiled over 700 longitudinal specimens from two independent cohorts (n = 65 and n = 73) of r/rLBCL patients treated with axicabtagene ciloleucel. A method for simultaneous profiling of circulating tumor DNA (ctDNA), cell-free CAR19 (cfCAR19) retroviral fragments, and cell-free T cell receptor rearrangements (cfTCR) enabled integration of tumor and both engineered and non-engineered T cell effector-mediated factors for assessing treatment failure and predicting outcomes.

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting.

Comparison of the effects of pre-dilution and post-dilution online hemodiafiltration on the levels of inflammatory markers, lymphocytes, and platelets.

Online hemodiafiltration (OL-HDF) is a blood purification therapy based on diffusion and ultrafiltration and is classified into two types according to the mode of addition of the substitution fluid: pre-dilution OL-HDF (pre-HDF) and post-dilution OL-HDF (post-HDF); we previously reported that pre-HDF is more biocompatible. However, we used lower blood and substitution flow rates in that study and may not have accurately simulated the treatment conditions used in Europe. In this study, we compared the biocompatibilities of the treatment conditions of pre-HDF, commonly used in Japan, and post-HDF, commonly used in Europe, to determine the most biocompatible treatment conditions.

Antibody-Based Treatment Approaches in Multiple Myeloma.

Purpose Of Review: The field of multiple myeloma treatment has entered a new era with antibody-based approaches in clinical practice. In this review, we focus on the clinical approaches of utilizing antibody-based modality, specifically monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell antibodies in the treatment of multiple myeloma.

Recent Findings: Three monoclonal antibodies (daratumumab, isatuximab, elotuzumab) and one anti-BCMA (B-cell maturation antigen) antibody-drug conjugate (belantamab mafodotin) have been approved by the FDA in the last 5 years for the treatment of multiple myeloma.

Neuroscience: A Face's Journey through Space and Time.

Faces are complex objects of great variety, which the visual brain somehow manages to organize by similarity. Two such orderings in fact exist and one, a new study finds, is transformed into the other over time, enhancing a face's distinctiveness.

Convolutional neural networks explain tuning properties of anterior, but not middle, face-processing areas in macaque inferotemporal cortex.

Recent computational studies have emphasized layer-wise quantitative similarity between convolutional neural networks (CNNs) and the primate visual ventral stream. However, whether such similarity holds for the face-selective areas, a subsystem of the higher visual cortex, is not clear. Here, we extensively investigate whether CNNs exhibit tuning properties as previously observed in different macaque face areas.

Evaluation of low-volume post-dilution online hemodiafiltration with Japanese high-performance hemodiafilters.

Purpose: To assess the removal performance of low-volume post-hemodiafiltration (HDF) with Japanese hemodiafilters and the removal performance with 20 % reduction in the total dialysate flow rate (Qtotal).

Methods: Subjects were 8 patients undergoing pre-HDF. Study 1: Post-HDF was performed at a blood flow rate (Q) of 250 mL/min and a total volume of substitution fluid (Vs) of 12 L/session(s) for 4 hrs using Fineflux-210Seco (FIX), ABH-21PA (ABH), and NVF-21H (NVF).

Therapeutic effect of high-efficiency online hemodiafiltration for recurrent restless legs syndrome in dialysis patients.

Two dialysis patients developed recurrent restless legs syndrome. The clinical courses and the association between the α-microglobulin removal rate and the therapeutic effects of hemodiafiltration were analyzed. Case 1: a middle-aged woman was switched from predilution online hemodiafiltration to hemodialysis, following which the α-microglobulin removal rate decreased from 39.

A Pilot Study of FDG-PET/CT in Polycythemia Vera Using Global Analysis Techniques.

Objectives: Functional imaging presents a non-invasive process that may capture the hyper-metabolic nature of red bone marrow in myeloproliferative neoplasms, such as polycythemia vera (PV).

Methods: This study analyzed the FDG-PET/CT scans (n=12) of six patients diagnosed with PV and six age-sex matched controls using a quantitative global analysis methodology.

Results: All PV patients had elevated activities in the bone marrow of each skeletal structure as compared to matched controls with respect to mean standardized uptake value (femoral neck p=0.

ZIP kinase phosphorylated and activated by Rho kinase/ROCK contributes to cytokinesis in mammalian cultured cells.

Cytokinesis of animal cells requires contraction of a contractile ring, composed of actin filaments and myosin II filaments. Phosphorylation of myosin II regulatory light chain (MRLC) promotes contraction of the actomyosin ring by activating myosin II motor activity. Both Rho-associated coiled-coil kinase (Rho kinase/ROCK) and Zipper-interacting protein kinase (ZIP kinase/ZIPK) have been reported to phosphorylate MRLC at the contractile ring.

α-Diimine-Niobium Complex-Catalyzed Deoxychlorination of Benzyl Ethers with Silicon Tetrachloride.

α-Diimine niobium complexes serve as catalysts for deoxygenation of benzyl ethers by silicon tetrachloride (SiCl) to cleanly give two equivalents of the corresponding benzyl chlorides, where SiCl has the dual function of oxygen scavenger and chloride source with the formation of a silyl ether or silica as the only byproduct. The reaction mechanism has two successive trans-etherification steps that are mediated by the niobium catalyst, first forming one equivalent of benzyl chloride along with the corresponding silyl ether intermediate that undergoes the same reaction pathway to give the second equivalent of benzyl chloride and silyl ether.

Iron deficiency in heart failure, an underdiagnosed and undertreated condition during hospitalization.

Heart failure (HF) is a chronic medical condition affecting an estimated 1-2% of the world's population, and as many as 10% of patients age 65 and above. Among patients with HF, iron deficiency (ID) has an estimated prevalence of 30-83%, often without concomitant anemia. Thus, ID in HF is often underdiagnosed unless actively sought after.

Hydrodehalogenation of alkyl halides catalyzed by a trichloroniobium complex with a redox active α-diimine ligand.

A high-valent d niobium(v) complex, (α-diimine)NbCl (1), bearing a dianionic redox-active α-diimine ligand served as a catalyst for a hydrodehalogenation reaction of alkyl halides in the presence of PhSiH. During the catalytic reaction, the redox-active α-diimine ligand allowed the complex to reversibly release and accept one-electron through switching its coordination mode between a dianionic folded form and a monoanionic planar one.