Excessive neutrophil recruitment promotes typical T-helper 17 responses in Coronavirus disease 2019 patients.

Coronavirus disease 2019 (COVID-19) is caused by a recently identified virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease is a pandemic. Although the hallmarks of severe COVID-19 have been established, the underlying mechanisms that promote severe pathology have not been thoroughly studied. A better understanding of the immune response in severe COVID-19 patients may help guide the development of therapeutic strategies and predict immuno-pathogenicity.

Sepsis in cancer patients residing in Zimbabwe: spectrum of bacterial and fungal aetiologies and their antimicrobial susceptibility patterns.

Background: Cancer and sepsis comorbidity is a major public health problem in most parts of the world including Zimbabwe. The microbial aetiologies of sepsis and their antibiograms vary with time and locations. Knowledge on local microbial aetiologies of sepsis and their susceptibility patterns is critical in guiding empirical antimicrobial treatment choices.

Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression.

RAS mutations occur frequently in multiple myeloma (MM), but apart from driving progression, they can also stimulate antitumor effects by activating tumor-suppressive RASSF proteins. Although this family of death effector molecules are often silenced in cancers, functional data about RASSF proteins in MM are lacking. Here, we report that is downregulated during MM progression and correlates with a poor prognosis.

Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP R-CHOP in the phase 3 LYM-3002 study.

In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7 14.4 months with R-CHOP; <0.

Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials.

Unlabelled: Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis.

Spontaneous chronic subdural hematomas in human immunodeficiency virus-infected patients with normal platelet count and no appreciable brain atrophy: Two case reports and review of literature.

Background: Chronic subdural hematomas (CSDHs) usually occur in elderly patients following minor head trauma. Their occurrence is usually linked to cerebral atrophy secondary to alcohol, old age, or human immunodeficiency virus (HIV) infection. Spontaneous CSDHs have also been documented but are rare.

Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma.

Background: Previous results from an interim analysis of an open-label, randomized, phase 3 study demonstrated that bortezomib combined with pegylated liposomal doxorubicin (PLD) was superior to bortezomib monotherapy in patients with relapsed/refractory multiple myeloma who had previously received one or more lines of therapy. Protocol-defined final survival data from that study are provided here.

Methods: Patients were randomized (1:1) to receive either bortezomib alone (1.

Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis.

CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report.

Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials.

Purpose: To characterize efficacy and safety of bortezomib-based versus nonbortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma.

Patients And Methods: Patient-level data from the IFM 2005-01 (bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

Purpose: Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study.

Experimental Design: A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective.

The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP.

Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma.

Purpose: This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies.

Patients And Methods: In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients.

Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma.

Purpose: Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety.

Patients And Methods: Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy-autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.

Pharmacokinetic, pharmacodynamic and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma.

Background And Objectives: The proteasome inhibitor bortezomib is approved for the treatment of multiple myeloma (MM) and, in the US, for the treatment of mantle cell lymphoma following at least one prior therapy; the recommended dose and schedule is 1.3 mg/m(2) on days 1, 4, 8 and 11 of 21-day cycles, and the approved routes of administration in the US prescribing information are by intravenous and, following a recent update, subcutaneous injection. Findings from a phase III study demonstrated that subcutaneous administration of bortezomib, using the same dose and schedule, resulted in similar efficacy with an improved systemic safety profile (including significantly lower rates of peripheral neuropathy) versus intravenous bortezomib in patients with relapsed MM.

Phase II clinical trial of first or second-line treatment with bortezomib in patients with malignant pleural mesothelioma.

Based on promising preclinical efficacy of bortezomib in mesothelioma, a single-arm phase II trial (Ireland Cooperative Oncology Research Group 05-10 study), with Simon's two-stage design, was undertaken to assess efficacy of bortezomib monotherapy in the first-line (poor performance status) and second-line settings. The Bcl-2 homology domain 3-only protein Noxa has been implicated as a key inducer of apoptosis by bortezomib. Thus, in a biomarker research substudy, we hypothesized that deficiency in Noxa expression might correlate with resistance.

Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma.

The phase III MMY-3021 study compared safety and efficacy of subcutaneous versus intravenous administration of the proteasome inhibitor bortezomib in patients with relapsed myeloma. The initial report demonstrated non-inferior efficacy with subcutaneous versus intravenous bortezomib for the primary end point: overall response rate after four cycles of single-agent bortezomib. We report updated outcome analyses after prolonged follow up.

Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Purpose: This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT).

Patients And Methods: Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks).

Health-related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: results from the VISTA trial.

Objectives: The phase 3 VISTA study (ClinicalTrials.gov NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone (MP) but also increased toxicity.

Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study.

This first prospective phase 2 study of single-agent bortezomib in relapsed primary systemic AL amyloidosis evaluated the recommended (maximum planned) doses identified in phase 1 testing (1.6 mg/m² once weekly [days 1, 8, 15, and 22; 35-day cycles]; 1.3 mg/m² twice weekly [days 1, 4, 8, and 11; 21-day cycles]).

Characterization of haematological parameters with bortezomib-melphalan-prednisone versus melphalan-prednisone in newly diagnosed myeloma, with evaluation of long-term outcomes and risk of thromboembolic events with use of erythropoiesis-stimulating agents: analysis of the VISTA trial.

Although haematological toxicities, such as anaemia, are common in multiple myeloma (MM), no clear consensus exists on the use and impact of erythropoiesis-stimulating agents (ESA) on outcomes in MM. This analysis characterizes haematological toxicities and associated interventions in the phase III VISTA (Velcade(®) as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone) study of bortezomib plus melphalan/prednisone (VMP, n = 344) versus MP (n = 338) in previously untreated MM patients ineligible for high-dose therapy, and evaluates the impact of ESA use or red-blood-cell (RBC) transfusions on outcomes and thromboembolic risk. Incidence of haematological toxicities was similar with VMP and MP; similar rates of interventions and associated complications (e.

Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma.

Objectives:   Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment.

Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study.

Objectives: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone.

Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2), days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m(2), days 1-4, cycles 1-9; and prednisone 60 mg/m(2), days 1-4, cycles 1-9).

Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone.

The phase 3 Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone study in newly diagnosed multiple myeloma patients ineligible for high-dose therapy demonstrated that bortezomib-melphalan-prednisone (VMP) was superior to melphalan-prednisone across all efficacy end points. We assessed the prognostic impact of response on time-to-event parameters in the intent-to-treat population. Patients received nine 6-week cycles of treatment.

Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial.

Purpose: The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies.

Patients And Methods: Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338).

Results: With a median follow-up of 36.

VMP (Bortezomib, Melphalan, and Prednisone) is active and well tolerated in newly diagnosed patients with multiple myeloma with moderately impaired renal function, and results in reversal of renal impairment: cohort analysis of the phase III VISTA study.

PURPOSE To assess bortezomib plus melphalan and prednisone (VMP) and melphalan and prednisone (MP) in previously untreated patients with multiple myeloma (MM) with renal impairment enrolled on the phase III VISTA study, and to evaluate renal impairment reversibility. PATIENTS AND METHODS Patients received nine 6-week cycles of VMP (bortezomib 1.3 mg/m(2), melphalan 9 mg/m(2), prednisone 60 mg/m(2)) or MP.