Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma.

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial.

Non-Toxicological Role of Aryl Hydrocarbon Receptor in Obesity-Associated Multiple Myeloma Cell Growth and Survival.

Obesity is not only a risk factor for multiple myeloma (MM) incidence, but it is also associated with an increased risk of progression from myeloma precursors-monoclonal gammopathy of undetermined significance-and smoldering myeloma. Adipocytes in the bone marrow (BMAs) microenvironment have been shown to facilitate MM cell growth via secreted factors, but the nature of these secreted factors and their mechanism of action have not been fully elucidated. The elevated expression of aryl hydrocarbon receptor (AhR) is associated with a variety of different cancers, including MM; however, the role of AhR activity in obesity-associated MM cell growth and survival has not been explored.

Creating Equitable and Inclusive Clinical Trials for Multiple Myeloma.

Black and Latino/Hispanic populations are disproportionately impacted by multiple myeloma (MM) in the United States and are underrepresented in many clinical trials. The Multiple Myeloma Research Foundation sponsored a 1-day workshop of 46 experts spanning the ecosystem of MM research and care, including government, academia, nonprofits, pharma/biotech, community partners, and retail pharmacy. Specific, tangible steps to overcome the well-documented barriers to improving the diversity and inclusivity of clinical trials were discussed, including broadening inclusion/exclusion criteria, reducing the financial and other burdens of trial participants, selecting diverse study sites, including implicit bias training, and taking steps to empower patients.

A Typical Presentation of an Atypical Condition: Hepatic Angiosarcoma With Peritoneal Bleed.

Hepatic angiosarcoma (HA) is a rare primary malignancy of hepatic endothelial and fibroblastic vascular tissue origin. Patients typically present with vague constitutional symptoms of fatigue, weight loss, abdominal pain, and ascites. Hemoperitoneum is a frequent clinical manifestation of HA associated with higher mortality and is underrecognized.

Multiple Myeloma for the Primary Care Provider: A Practical Review to Promote Earlier Diagnosis Among Diverse Populations.

Multiple myeloma is the second most common hematologic malignancy in the United States and the most common hematologic malignancy among Blacks/African Americans. Delay in diagnosis is common and has been associated with inferior disease-free survival and increased rates of myeloma-related complications. Despite a roughly 2-times higher risk of multiple myeloma, diagnostic delay appears more common, and improvements in 5-year survival rates have been slower among Blacks/African Americans than their White counterparts.

Preferences and Priorities for Relapsed Multiple Myeloma Treatments Among Patients and Caregivers in the United States.

Introduction/background: This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM).

Materials And Methods: A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration.

Symptom Burden, Perceived Control, and Quality of Life Among Patients Living With Multiple Myeloma.

Background: New therapies for multiple myeloma (MM) have improved survival rates but often expose patients to heightened toxicities and prolonged treatment, leading to increasing complications and side effects. We evaluated the association between symptom burden, perceived control over illness, and quality of life (QoL) among a national sample of patients with MM.

Methods: For this observational, cross-sectional study, we used data from the Cancer Experience Registry research initiative to examine symptom- and functioning-related concerns among 289 patients with MM across the illness trajectory.

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.

Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation trial of twice-weekly selinexor in combination with carfilzomib and dexamethasone (SKd) to determine maximum tolerated dose in patients with RRMM (N = 21), with an expansion cohort to assess activity in carfilzomib-refractory disease and identify a recommended phase II dose (RP2D).

Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma.

Purpose: The major cause of death in aggressive lymphoma is relapse or nonresponse to initial therapy. Lenalidomide has activity in a variety of hematologic malignancies, including non-Hodgkin's lymphoma (NHL). We report the results of a phase II, single-arm, multicenter trial evaluating the safety and efficacy of lenalidomide oral monotherapy in patients with relapsed or refractory aggressive NHL.

Circulating endothelial cells in patients with chronic lymphocytic leukemia.

Angiogenesis is increased in B-cell chronic lymphocytic leukemia (B-CLL). We wanted to quantify and characterize the circulating endothelial cells (CECs) in patients with B-CLL and correlate with plasma angiogenesis-related factors. Using a four-color flow cytometry, we prospectively analyzed the CEC in the whole blood of 20 healthy controls and 20 patients with B-CLL.

Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells.

Caveolae, specialized flask-shaped lipid rafts on the cell surface, are composed of cholesterol, sphingolipids, and structural proteins termed caveolins; functionally, these plasma membrane microdomains have been implicated in signal transduction and transmembrane transport. In the present study, we examined the role of caveolin-1 in multiple myeloma cells. We show for the first time that caveolin-1, which is usually absent in blood cells, is expressed in multiple myeloma cells.

Novel therapies for multiple myeloma.

Multiple myeloma (MM) continues to evade cure by conventional therapies, increasing the urgency for new, biologically based treatments. Reviewed in this discussion are novel chemotherapies under clinical trial that capitalize upon greater comprehension of tumor pathophysiology. In targeting tumor biology, these therapies serve as a model of treatment with great potential for improving outcomes in patients with MM.