ARPES signatures of few-layer twistronic graphenes

Diverse emergent correlated electron phenomena have been observed in twisted graphene layers due to electronic interactions with the moir\'e superlattice potential. Many electronic structure predictions have been reported exploring this new field, but with few momentum-resolved electronic structure measurements to test them. Here we use angle-resolved photoemission spectroscopy (ARPES) to study the twist-dependent ($1^\circ < \theta < 8^\circ$) electronic band structure of few-layer graphenes, including twisted bilayer, monolayer-on-bilayer, and double-bilayer graphene (tDBG). Direct comparison is made between experiment and theory, using a hybrid $\textbf{k}\cdot\textbf{p}$ model for interlayer coupling and implementing photon-energy-dependent phase shifts for photo-electrons from consecutive layers to simulate ARPES spectra. Quantitative agreement between experiment and theory is found across twist angles, stacking geometries, and back-gate voltages, validating the models and revealing displacement field induced gap openings in twisted graphenes. However, for tDBG at $\theta=1.5\pm0.2^\circ$, close to the predicted magic-angle of $\theta=1.3^\circ$, a flat band is found near the Fermi-level with measured bandwidth of $E_w = 31\pm5$ meV. Analysis of the gap between the flat band and the next valence band shows significant deviations between experiment ($\Delta_h=46\pm5$meV) and the theoretical model ($\Delta_h=5$meV), indicative of the importance of lattice relaxation in this regime

CyBorD-DARA is potent initial induction for MM and enhances ADCP: Initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

CyBorD DARA as induction is well tolerated and induces deep responses when used in conjunction with ASCT for MM.Mechanism of action studies indicate that CyBorD DARA enhances macrophage activation, which may play a role in its clinical efficacy. Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810

New developments in the treatment of multiple myeloma &ndash; clinical utility of daratumumab

Cian McEllistrim,1 Janusz Krawczyk,1 Michael E O&rsquo;Dwyer1,2 1Department of Hematology, University Hospital Galway, 2Apoptosis Research Centre, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland Abstract: Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups. Keywords: multiple myeloma, monoclonal antibodies, daratumumab, immunotherapy, CD38, minimal residual diseas