Targeting B-cell maturation antigen for treatment and monitoring of relapsed/refractory multiple myeloma patients: a comprehensive review.

Despite major therapeutic advancements in recent years, multiple myeloma (MM) remains an incurable disease with nearly all patients experiencing relapsed and refractory disease over the course of treatment. Extending the duration and durability of clinical responses will necessitate the development of therapeutics with novel targets that are capable of robustly and specifically eliminating myeloma cells. B-cell maturation antigen (BCMA) is a membrane-bound protein expressed predominantly on malignant plasma cells and has recently been the target of several novel therapeutics to treat MM patients.

Serum B-Cell Maturation Antigen Reflects Disease Status in a Patient Who Developed Nonsecretory Multiple Myeloma: A Case Report.

Introduction: Multiple myeloma (MM) is an incurable bone marrow (BM)-based cancer involving clonal plasma cells. Most patients show elevated levels of serum monoclonal protein (sMP) and kappa or lambda serum free light chains (sFLCs) at diagnosis. However, around 1-2% of patients, termed nonsecretory, do not produce these biomarkers.

Medication development for AUD: A systematic review of clinical trial methodology.

Refining clinical trial methodology has become increasingly important as study design is shown to influence treatment efficacy. To maximize the efficiency of randomized clinical trials (RCTs), researchers aim to establish standardized practices. The goal of this systematic review is to describe methodological practices of clinical trials for alcohol use disorder (AUD) over the past 40 years.

Response to Letter to the Editors regarding 'A Meta-Regression of Trial Features Predicting the Effects of Alcohol Use Disorder Pharmacotherapies on Drinking Outcomes in Randomized Clinical Trials: A Secondary Data Analysis'.

The Letter to the Editors regarding our article was reviewed. The take-home message is that substantively, the authors of the letter are referencing a paper that asks a different research question in a different set of studies. When we ask different questions, we are not surprised when we reach different answers.

Clinical Outcomes and Serum B-Cell Maturation Antigen Levels in a Real-World Unselected Population of Newly Diagnosed Multiple Myeloma Patients.

Background: Progression-free survival (PFS) and overall survival (OS) of newly diagnosed multiple myeloma (MM) patients have been widely published in the clinical trials setting, but data published from real-world settings are limited.

Objective: We determined the survival and factors that predict outcomes among 161 unselected, newly diagnosed MM patients whose frontline therapy was started at a single clinic specializing in the treatment of this B-cell malignancy.

Patients And Methods: None of these patients underwent an autologous stem cell transplantation as part of their initial therapy and the population had a high proportion (35%) of cytogenetic high-risk patients.

The incidence of translocation t(11;14) among patients with multiple myeloma in a single clinic.

Objectives: Data regarding bone marrow (BM) sampling and cytogenetic testing rates for identification of translocation (11q13;14q32) and their changes over time in a multiple myeloma (MM) population are limited. We analyzed these metrics at a clinic specializing in the treatment of MM.

Methods: A total of 760 BM aspirate samples from 351 patients were collected between August 2004 and October 2021.

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study.

Objectives: Isatuximab is approved for treatment of relapsed/refractory multiple myeloma (RRMM) with dexamethasone and carfilzomib or pomalidomide. Patients receiving these three-drug regimens have exhibited more Grade ≥ 3 adverse events (AEs) compared to the two-drug class combination of isatuximab and steroids alone. Thus, this single-center retrospective study investigated the efficacy of isatuximab with dexamethasone and methylprednisolone (ISAdm) for RRMM patients showing only biochemical progression (BP) of their disease.

High risk lung nodule: A multidisciplinary approach to diagnosis and management.

Pulmonary nodules are often discovered incidentally during CT scans performed for other reasons. While the vast majority of nodules are benign, a small percentage may represent early-stage lung cancer with the potential for curative treatments. With the growing use of CT for both clinical purposes and lung cancer screening, the number of pulmonary nodules detected is expected to increase substantially.

Loss of anti-spike antibodies following mRNA vaccination for COVID-19 among patients with multiple myeloma.

Background: Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID-19. Little is known regarding their vaccine-induced antibody levels over time.

Methods: We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations.

Third dose of an mRNA COVID-19 vaccine for patients with multiple myeloma.

We have reported that IgG antibody responses following two mRNA COVID-19 vaccinations are impaired among patients with multiple myeloma (MM). In the current study, sixty-seven patients with MM were tested for anti-spike IgG antibodies 0-60 days prior to their first vaccination, 14-28 days following the second dose, and both before and 14-28 days after their third dose of the mRNA-1273 or BNT162b2 vaccines. After the first two doses, most patients' (93 %) antibody levels declined to ineffective levels (<250 BAU/mL) prior to their third dose (D3).

Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma.

Although Janus kinase (JAK) inhibitors have demonstrated efficacy for treating autoimmune disorders and myeloproliferative neoplasms, their efficacy in treating other types of cancer has not been clearly demonstrated. We evaluated oral ruxolitinib (15 mg twice daily) with oral methylprednisolone (40 mg every other day) for multiple myeloma (MM) patients with progressive disease who had received a proteasome inhibitor, lenalidomide, glucocorticosteroids and three or more prior regimens. All of the planned 29 patients had been enrolled with follow-up until 28 April 2022.

Implementation of a Virtual Huddle to Support Patient Care During the COVID-19 Pandemic.

Background: During a surge of COVID-19 cases, the volume of acute care patients with hypoxemic respiratory failure placed a high burden of responsibility on internal medicine, pulmonary and critical care medicine, and clinical pharmacy services.

Observations: We describe the COVID-19 Tele-Huddle Program, a novel approach to communication between key stakeholders in COVID-19 patient care through a daily video conferencing huddle. The program was implemented during a 4-week surge in COVID-19 cases at a large, academic medical center in Houston, Texas.

The JAK1/2 inhibitor ruxolitinib downregulates the immune checkpoint protein B7H3 in multiple myeloma.

We hypothesized that ruxolitinib may inhibit the immune checkpoint protein, B7H3; and, thus, investigated its effects on this immune inhibitor using multiple myeloma (MM) cell lines, bone marrow (BM) mononuclear cells from MM patients and human MM LAG -1A xenografts. Ruxolitinib reduced B7H3 gene and protein expression and increased IL-2 and CD8 gene expression. These results suggest that ruxolitinib inhibition of B7H3 may restore exhausted T-cell activity in the MM BM tumor microenvironment.

A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients.

Ruxolitinib with lenalidomide and dexamethasone shows anti-myeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma (MM) cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide.

Challenges in initiating a lung cancer screening program: Experiences from two VA medical centers.

Establishing a lung cancer screening (LCS) program is an important endeavor that delivers life-saving healthcare to an at-risk population. However, developing a comprehensive LCS program requires critical elements including obtaining institutional level buy-in, hiring necessary personnel, developing appropriate infrastructure and actively engaging primary care providers, subspecialty services, and radiology. The process required to connect such services to deliver an organized LCS program that reaches all eligible candidates must be individualized to each institution's needs and infrastructure.

A Meta-Regression of Trial Features Predicting the Effects of Alcohol Use Disorder Pharmacotherapies on Drinking Outcomes in Randomized Clinical Trials: A Secondary Data Analysis.

Aims: To test whether two critical design features, inclusion criteria of required pre-trial abstinence and pre-trial alcohol use disorder (AUD) diagnosis, predict the likelihood of detecting treatment effects in AUD pharmacotherapy trials.

Methods: This secondary data analysis used data collected from a literature review to identify randomized controlled pharmacotherapy trials for AUD. Treatment outcomes were selected into abstinence and no heavy drinking.

Use of serum B-cell maturation antigen levels to predict outcomes for myeloma patients treated with ruxolitinib, lenalidomide and methylprednisolone.

Previous retrospective studies have shown that serum B-cell maturation antigen (sBCMA) levels predict outcomes among patients with multiple myeloma (MM) undergoing new treatments. Specifically, baseline levels and changes during treatment of this protein predict both progression free survival (PFS) and overall survival. However, prospective studies are lacking evaluating sBCMA for determining outcomes among MM patients undergoing new treatments.

Severe breakthrough COVID-19 with a heavily mutated variant in a multiple myeloma patient 10 weeks after vaccination.

Background: Patients with multiple myeloma have unpredictable responses to vaccination for COVID-19. Anti-spike antibody levels can determine which patients develop antibodies at levels similar to healthy controls, and are a known correlate of protection.

Case Report: A multiple myeloma patient developed protective anti-spike antibodies after vaccination (608 IU/mL), but nonetheless developed severe breakthrough COVID-19 just 10 weeks following his second vaccination with mRNA-1273.

Response to mRNA vaccination for COVID-19 among patients with multiple myeloma.

Multiple myeloma (MM) patients are at higher risk for severe COVID-19. Their mRNA vaccination response against SARS-CoV-2 is unknown. Thus, we analyzed responses to mRNA vaccination against COVID-19 among these patients.

Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients.

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients.

Lifetime heavy drinking years predict alcohol use disorder severity over and above current alcohol use.

: Preclinical studies demonstrate that chronic and heavy alcohol use facilitates neuroadaptations that perpetuate addiction-like behaviors. In clinical studies, it is unclear whether the extent of heavy alcohol use over the lifetime contributes to alcohol use disorder (AUD) severity over and above current alcohol use patterns (i.e.

A meta-regression of methodological features that predict the effects of medications on the subjective response to alcohol.

Background: Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol.

Ibudilast, a neuroimmune modulator, reduces heavy drinking and alcohol cue-elicited neural activation: a randomized trial.

Ibudilast, a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE)-3, -4, -10, and -11, and macrophage migration inhibitory factor (MIF), shows promise as a novel pharmacotherapy for alcohol use disorder (AUD). However, the mechanisms of action underlying ibudilast's effects on the human brain remain largely unknown. Thus, the current study examined the efficacy of ibudilast to improve negative mood, reduce heavy drinking, and attenuate neural reward signals in individuals with AUD.