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PURPOSE There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10–3 in the VIALE-A trial. METHODS The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10–3 or 0.1%) with an estimated analytic sensitivity of 0.0037%-0.0027%. CRc, duration of remission (DoR), event-free survival (EFS), and overall survival (OS) were assessed. A multivariate Cox regression analysis identified prognostic factors associated with OS. RESULTS One hundred sixty-four of one hundred ninety (86%) patients with CRc were evaluable for MRD. MRD < 10–3 was achieved by 67 of 164 (41%), and 97 of 164 (59%) had MRD ≥ 10–3. The median DoR, EFS, and OS were not reached in patients with CRc and MRD < 10–3, and the 12-month estimates for DoR, EFS, and OS in this group were 81.2%, 83.2%, and 94.0%. Among patients with CRc and MRD ≥ 10–3, the median DoR, EFS, and OS were 9.7, 10.6, and 18.7 months. Multivariate analysis showed that CRc with MRD < 10–3 was a strong predictor of OS (adjusted hazard ratio = 0.285; 95% CI, 0.159 to 0.510; P < .001). CONCLUSION Patients who achieved CRc and MRD < 10–3 with venetoclax and azacitidine had longer DoR, EFS, and OS, than responding patients with MRD ≥ 10–3.

Biot's coefficient is one of the key parameters in estimating effective stresses, leading to understanding of the three stresses spatial distribution, namely vertical, minimum and maximum horizontal. Ultimately, these stresses shape up the behavior of a geomechanics model (either in 3D or in 1D). Thus, the robustness of any geomechanics model significantly depends on the precision of Biot's coefficient estimation. The proposed technique allows evaluating isotropic and anisotropic Biot's coefficients based on the log responses independent of the geological environment. The methodology is based on elastic moduli-minimization. In isotropic case, Bulk rock frame and Bulk rock grain moduli minimization produce the best fit to the measured Density, DTP and DTS. Then, isotropic Biot's coefficient can be computed directly. In the case of anisotropy, additional control on lamination is required. This can be achieved by comparing estimated laminated and dispersed clay volumes based on the anisotropic rock-physics model and derived from the Thomas-Stieber plot or any alternative lamination analysis technique. Anisotropy modeling allows to produce five independent VTI elastic moduli and as a result to compute anisotropic Biot's coefficient. The methodology has been tested in several fields: clastic (Western Siberia, Norwegian offshore, Argentina unconventional) and carbonates (Brazil, Middle East, North Sea chalks). It produces reliable results in all cases. This study shows good agreement of the Biot's coefficient computed from the proposed methodology with measurements of core-based Biot's coefficients. In practice, core-based Biot's coefficient measurements are rarely available and quite often done on a few samples, taken in the reservoir section only. The proposed methodology allows reliable estimates of Biot's coefficient for the entire wellbore section, where density and sonic logs are available. It utilizes a minimization technique instead of using geomechanics correlations. Thus, it is applicable for any rocks and geological settings and is not bounded to the area or formation compared to correlations specific to the particular formation. The novelty of the method is in the process of elastic-moduli minimization based on logs and allows direct extraction of the Biot's coefficient. Previous works were either concentrating on principles of the laboratory Biot's coefficient measurements or focusing on the correlations derived from core tests. Correlation derivation requires a significant number of core tests conducted for the same geological settings. However, the proposed methodology requires a few core samples for Q.C. purposes only.

Oil and gas companies’ future production profile is shaped by their exploration strategy and resource base development. Gazprom Neft's production profile will include 40% of current exploration projects by 2030. Geological exploration, on the other hand, is a high-risk business because it involves a lot of uncertainty due to the geological complexity of the targets being explored, as well as a lot of risky capital. Taking these factors into account, the Company will need to expand its exploration function as well as its approaches to managing exploration projects in order to meet its lofty aims. To determine the key areas of growth and a strategy for the exploration function development in the coming years, it was decided to first analyze the geological exploration activity in the Company in 2010 – 2020 period. The knowledge of achievements, success stories, and development areas is the fulcrum for future victories. Therefore, retrospective analysis is an important tool for the development of any system of activity - individual, organization, or state.

Patients with relapsed/refractory multiple myeloma (RRMM) experience several relapses, and become refractory to successive therapies. In the ICARIA-MM trial (NCT02990338), isatuximab plus pomalidomide-dexamethasone prolonged median progression-free survival (PFS) in patients with RRMM. This subgroup analysis of ICARIA-MM assessed the treatment benefit of isatuximab by prior lines of therapy and refractory status. A total of 307 patients were randomized to isatuximab-pomalidomide-dexamethasone (n = 154) or pomalidomide-dexamethasone (n = 153). Isatuximab (10 mg/kg intravenously) was given weekly in the first 28-day cycle, then every other week. Standard pomalidomide-dexamethasone doses were given. PFS was assessed by prior lines and refractory status. Overall, 102 (66 %) patients receiving isatuximab-pomalidomide-dexamethasone and 101 (66 %) patients receiving pomalidomide-dexamethasone had received 2–3 prior lines; 52 (34 %) and 52 (34 %) had received >3 prior lines, respectively. Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who received 2–3 prior lines of therapy (12.3 vs. 7.8 months) and >3 prior lines of therapy (9.4 vs. 4.3 months). Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who were lenalidomide-refractory (11.4 vs. 5.6 months), lenalidomide-refractory at last line (11.6 vs. 5.7 months), refractory to a proteasome inhibitor (PI) (11.4 vs. 5.6 months), and double-refractory (11.2 vs. 4.8 months). Overall response rate (ORR) in patients receiving isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone was 59.0 % versus 31.4 % in lenalidomide-refractory; 60.2 % versus 32.2 % in PI-refractory; and 58.6 % versus 29.9 % in double-refractory patients. Isatuximab-pomalidomide-dexamethasone improved PFS and ORR regardless of prior lines of therapy or refractory status, consistent with the benefit in the overall population. © 2021 The Authors, Amgen Bristol-Myers Squibb, BMS Pfizer Roche Sanofi Celgene Takeda Pharmaceutical Company, TPC Janssen Pharmaceuticals, SB reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, and Janssen; and reports a consultancy/advisory role for Celgene, Janssen, Karyopharm, and Takeda. VV reports a consultancy/advisory role for Astellas, Biocad, Bristol-Myers Squibb, Janssen, Roche, Sanofi, and Takeda. VM reports a consultancy/advisory role for Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. LK reports honoraria from Amgen, Celgene, Janssen, and Takeda; a consultancy/advisory role for Amgen, Celgene, Janssen, and Takeda; and travel support from Amgen and Janssen. MP reports honoraria from Celgene, Pfizer, and Takeda; consultancy/advisory role for Amgen, Celgene, Janssen, Roche, and Takeda; and research funding from Amgen, Celgene, Janssen, Pfizer, Roche, and Takeda. PGR reports a consultancy/advisory role for Amgen, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda; and research funding from Bristol-Myers Squibb, Celgene, Oncopeptides, and Takeda. LP, FV, KW, LB, and YK have no disclosures. FC, SLG, FM, and HvdV are employees of Sanofi., The ICARIA-MM study was sponsored by Sanofi . The authors thank the participating patients and their families, and the study centers and investigators for their contributions to the study. Medical writing support was provided by Stephanie Brillhart, Julian Ball, and Smitha Reddy of Elevate Medical Affairs E (Fairfield, CT, USA), and funded by Sanofi (Cambridge, MA, USA).

BACKGROUND: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. METHODS: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (

We provide direct experimental comparison of the optoacoustic imaging performance of two different 64-element linear detector array (LDA) units based on polyvinylidene difluoride (PVDF) films. The first LDA unit was based on traditional flexible circuit (FC) technology and consisted of an FC glued to the nonmetalized signal surface of a 28-μm-thick PVDF film providing 300 / 80-μm axial resolution/lateral resolution (AR/LR) and 0.4-kPa noise equivalent pressure of its single element. The other LDA unit was manufactured using a technology of low-temperature photolithographic etching (PE) of a signal electrode onto a 25-μm-thick PVDF film providing 300 / 40-μm AR/LR and 1 kPa noise equivalent pressure. As compared with a previously reported LDA unit based on a 100-μm PVDF thick film, the main advantage of using the thinner PVDF films was 10-fold improvement in axial resolution, whereas the main drawback was 10-fold increased noise equivalent pressure. In terms of in vivo imaging performance, higher bandwidth of PE LDA probe was more important than the higher sensitivity of FC LDA unit.

Minimization of disparities between welltest and log-derived average permeabilities has always been an issue, particularly in carbonates where complex pore structures add on challenges to permeability estimation from wireline log data. The disagreement between permeability averages from logs and well tests originates from the combined effects of measurement-scale of static porosity components for permeability models, dual flow system of fractures and matrix, tensorial nature of permeability and the averaging techniques used.The proposed workflow exploits rock-physics templates to identify and to quantify secondary porosity. Rock-physics templates employ conventionally derived total porosity and shear modulus as inputs. Fracture and vug porosity identified by the proposed workflow through rock-physics agree with other qualitative and quantitative evidences of non-primary porosity obtained from NMR, Image logs and core data1. Matrix and connected-vug permeabilities are computed, calibrated and integrated via "Chen-Jacobi" connectivity-driven model2 by using NMR and acoustic log data. Fracture permeability is estimated from "fracture aperture" and fracture-porosity by using image log data and rock-physics algorithms. The final permeability profile is computed with a selective-replacement step. This step ensures that in co-presence of matrix, connected vugs and fracture permeabilities at a given discrete depth level, the greater one would dominate and replace the lesser one. The final step in efforts of lessening the disparity between averages of wireline-driven and well test/DST permeabilities for a given interval is the usage of proposed averaging technique for the integrated wireline-driven permeability profile.The rock-physics templates used in this study combine Kuster and Toksoz3 "inclusions" theory with the Dvorkin-Nur4 granular media model (1996). We have observed appreciable correlations between secondary porosity driven from shear velocities against the secondary porosity determined from NMR and Image logs and core data. These correlations further provide routes for newer permeability models that can be solely based on the rock-physics.Comparisons of permeability averages computed from wireline-driven permeability profiles against DST or welltest permeability showed significant improvements toward parity via proposed methodology and averaging technique. The workflow presented in this study is to guide the reader through numerous steps of the proposed algorithm in detail.