Publications by authors named "Alfred Chung"

We investigated BCMA-directed CART in patients with relapsed or refractory multiple myeloma (RRMM) and CNS involvement. Ten patients who received either ide-cel (n=6) or cilta-cel (n=4) were included in this analysis. Patients had brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease evident on either MRI (100%) and/or CSF (40%).

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No randomized trial has directly compared daratumumab and lenalidomide (D-R) maintenance therapy versus standard-of-care lenalidomide (R) alone post-transplant. Here, we report the primary results of the phase 3 AURIGA study evaluating D-R versus R maintenance in NDMM patients who were in ≥very good partial response, minimal residual disease (MRD; threshold 10-5) positive, and anti-CD38 naïve post-transplant. Patients were randomized 1:1 to D-R or R maintenance for up to 36 cycles.

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For patients with relapsed/refractory multiple myeloma with a relapse after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAbs) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies.

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Patients receiving autologous chimeric antigen receptor T cell (CAR-T) therapy for multiple myeloma (MM) may require bridging therapy (BT) before CAR-T infusion to maintain some level of disease control. Alkylators, such as cyclophosphamide (Cy), are often used in regimens, either in high-intensity regimens, such as modified hyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), or once-weekly regimens, such as KCd (carfilzomib, cyclophosphamide, and dexamethasone). However, there is no consensus regarding the optimal BT alkylator dose intensity in MM.

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International Myeloma Working Group (IMWG) response criteria require refrigerated 24-hour urine specimens for most patients. However, given that serum free light chain testing has been shown to outperform 24-hour urine immunofixation as a prognostic marker, the importance of maintaining urine testing options or requirements within each level of IMWG response criteria has not been investigated. We analyzed responses to induction therapy for all transplant-eligible patients with multiple myeloma at our institution over a 3-year period using traditional versus 'urine-free' IMWG response criteria (where references to urine were removed from the descriptions for every depth of response).

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Risks of B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy for patients with multiple myeloma (MM) include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, and infections. The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium, which may be more prevalent in older patients, have not been fully analyzed. We wanted to analyze the efficacy and safety of BCMA CAR-T therapy among older patients (age ≥70 at infusion) versus younger patients with MM.

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The CD38-targeting monoclonal antibodies (CD38 mAbs) are well-established therapies in multiple myeloma (MM), but responses to treatment are not always deep or durable. Natural killer (NK) cells deficient in Fc epsilon receptor gamma subunits, known as g-NK cells, are found in higher numbers among individuals exposed to cytomegalovirus (CMV) and are able to potentiate the efficacy of daratumumab in vivo. Here, we present a single-centre, retrospective analysis of 136 patients with MM with known CMV serostatus who received a regimen containing a CD38 mAb (93.

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Light chain amyloidosis (AL) is a plasma cell dyscrasia characterized by organ dysfunction, morbidity, and early mortality. Daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone is now standard frontline AL therapy; however, not all patients are candidates for this intensive regimen. Given the potency of Daratumumab, we evaluated an alternative frontline regimen: daratumumab, bortezomib, and limited-duration dexamethasone (Dara-Vd).

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Background: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting.

Objectives: The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management.

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We investigated antibody and coronavirus disease 2019 (COVID-19)-specific T-cell mediated responses via ultra-deep immunosequencing of the T-cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike-receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ-78436735. A total of 56 patients underwent TCR immunosequencing after vaccination.

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Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking.

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Therapy-related myeloid neoplasms (t-MN), including therapy-related acute myeloid leukaemia and myelodysplastic syndrome, are second primary malignancies (SPM) that are of growing importance as patients with plasma cell disorders (PCD) such as multiple myeloma (MM) are living longer with more effective therapies. Both patient-specific and treatment-specific factors likely impact the risk of t-MN development after diagnosis and treatment of PCD. Alkylating chemotherapy, especially melphalan, has been strongly tied to the risk of t-MN.

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Background: Dermatomyositis, an inflammatory myopathy with cutaneous involvement, is associated with malignancy and often manifests paraneoplastically. While co-occurrence with small cell carcinoma is well attested, primary lung adenocarcinoma, which may present as focal ground-glass opacification on computed tomography of the thorax, is less frequently coincident.

Case Presentation: We report the case of a 72-year-old female patient with dermatomyositis - treated with a combination of prednisone, methotrexate, and intravenous immunoglobulin - and an indolent, subsolid, non-hypermetabolic pulmonary lesion, which was determined to be invasive primary lung adenocarcinoma.

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FLT3 fusions are associated with myeloid and lymphoid neoplasms with eosinophilia. We describe a patient presenting with clinicopathologic features of both chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) and systemic mastocytosis (SM). The bone marrow demonstrated a myeloproliferative neoplasm with eosinophilia and aggregates of atypical mast cells.

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An eight-sensor array coupling a chemoselective room-temperature ionic liquid (RTIL) with quartz crystal microbalance (QCM) transduction is presented in this work in order to demonstrate the power of this approach in differentiating closely related analytes in sensory devices. The underlying mechanism behind the specific sensory response was explored by (i) studying mass loading and viscoelasticity effects of the sensing layers, predominantly through variation in damping impedance, the combination of which determines the sensitivity; (ii) creation of a solvation model based on Abraham's solvation descriptors which reveals the fact that polarizability and lipophilicity are the main factors influencing the dissolution of gas analytes into the RTILs; and (iii) determination of enthalpy and entropy values for the studied interactions and comparison via a simulation model, which is also effective for pattern discrimination, in order to establish a foundation for the analytical scientist as well as inspiration for synthetic pathways and innovative research into next-generation sensory approaches. The reported sensors displayed an excellent sensitivity with detection limit of <0.

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Interfacing cells with nanomaterials such as graphene, nanowires, and carbon nanotubes is useful for the integration of cellular physiology with electrical read outs. Here we show the interfacing of graphene sheets on the surface of yeast cells, leading to electromechanical coupling between the sheets and the cells. The cells are viable after the interfacing.

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Polyglutamine repeats in proteins are highly correlated with amyloid formation and neurological disease. To better understand the molecular basis of glutamine repeat diseases, structural analysis of polyglutamine peptides as soluble monomers, oligomers, and insoluble amyloid fibrils is necessary. In this study, fluorescence resonance energy transfer (FRET) experiments and molecular dynamics simulations using different theoretical models of polyglutamine were conducted.

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Regulators of G protein signaling (RGS) proteins are potent negative modulators of G protein signaling and have been proposed as potential targets for small-molecule inhibitor development. We report a high-throughput time-resolved fluorescence resonance energy transfer screen to identify inhibitors of RGS4 and describe the first reversible small-molecule inhibitors of an RGS protein. Two closely related compounds, typified by CCG-63802 [((2E)-2-(1,3-benzothiazol-2-yl)-3-[9-methyl-2-(3-methylphenoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl]prop-2-enenitrile)], inhibit the interaction between RGS4 and Galpha(o) with an IC(50) value in the low micromolar range.

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Microwave-assisted solid-phase syntheses of six "difficult" peptides, H-VVSVV-NH(2) (3), H-VVVSVV-NH(2) (4), H-VIVIG-OH (5), H-TVTVTV-NH(2) (6), H-VKDGYI-NH(2) (7), and H-VKDVYI-NH(2) (8), were achieved utilizing N-(Fmoc-alpha-aminoacyl)benzotriazoles. Extension to the syntheses of Leu-enkephalin (9) and amyloid-beta (34-42) (10) demonstrates that this strategy comprises an efficient route to new and known "difficult" peptides.

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