Uncommon Presentation of Multiple Myeloma: Pleural Effusion and Extensive Extramedullary Involvement.

A 60-year-old female presented with abdominal pain, weight loss, and fatigue. Imaging revealed a pancreatic mass, bilateral pleural effusion, ascites, and lytic bony lesions. Investigations confirmed multiple myeloma with lambda light chain disease.

Prehabilitation Exercise Training to Target Improved Muscle Strength in Pretransplant Patients Diagnosed With Multiple Myeloma: Protocol for a Pilot Randomized Controlled Trial.

Background: Muscle mass and strength are severely compromised in patients diagnosed with multiple myeloma, such that the risk of poor overall survival increases as the prevalence of low muscle mass, also known as sarcopenia, increases. Additionally, at the time of autologous stem cell transplant (ASCT), 51% of patients experience low muscle mass and strength, which can prolong hospitalization and lead to increased risk of obesity, insulin resistance, lowered physical function, and poor quality of life.

Objective: The PROTECT (Prehabilitation Exercise Training in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation) trial will examine the preliminary effects of digitally supervised prehabilitative aerobic and resistance exercise on muscle strength in patients with multiple myeloma scheduled for ASCT.

Approaching Hypercalcemia in Monoclonal Gammopathy of Undetermined Significance: Insights from the iStopMM study.

Hypercalcemia in monoclonal gammopathy of undetermined significance (MGUS) presents a clinical challenge since it may indicate progression to multiple myeloma (MM) but could also be due to a multitude of unrelated disorders. To inform the approach to this clinical challenge, we conducted a nested cohort study within the iStopMM screening study. Of the 75,422 Icelanders aged 40 years and above who underwent screening for MGUS, we included 2,546 with MGUS who were in active follow-up, including regular serum calcium measurements.

A Monte-Carlo planning strategy for medical follow-up optimization: Illustration on multiple myeloma data.

Designing patient-specific follow-up strategies is key to personalized cancer care. Tools to assist doctors in treatment decisions and scheduling follow-ups based on patient preferences and medical data would be highly beneficial. These tools should incorporate realistic models of disease progression under treatment, multi-objective optimization of treatment strategies, and efficient algorithms to personalize follow-ups by considering patient history.

Single Cell RNA Sequencing Before and After Light Chain Escape Reveals Intra-patient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression.

High-risk multiple myeloma (MM) is genomically unstable, comprised of heterogeneous populations of tumor cells that evolve over time. Light chain escape (LCE) is a clinical phenomenon observed when light chains rise separately from M-spike values, implying divergent tumor evolution. We sought to understand LCE by performing high depth transcriptomic and phenotypic studies.

Distinguishing Daratumumab from Endogenous Monoclonal Proteins in Serum from Multiple Myeloma Patients Using an Automated Mass Spectrometry System.

Background: Therapeutic monoclonal antibodies (t-mAbs) may interfere with electrophoresis-based methods used to monitor multiple myeloma (MM), which can create inaccurate results. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is an alternative to gels distinguishing between endogenous M-proteins and t-mAbs based on molecular mass.

Methods: Serum samples (n = 109) from 34 MM patients receiving Dara-KRd were collected 14 or 28 days postdaratumumab administration.

A feasibility study of using virtual noncontrast images synthesized from dual-energy computed tomography for radiotherapy treatment planning.

Background: In the traditional computed tomography (CT) simulation process, patients need to undergo CT scans before and after injection of iodine-based contrast agent, resulting in a cumbersome workflow and additional imaging dose. Contrast-enhanced spectral CT can synthesize true contrast-enhanced (TCE) images and virtual noncontrast (VNC) images in a single scan without geometric misalignment. To improve work efficiency and reduce patients' imaging dose, we studied the feasibility of using VNC images for radiotherapy treatment planning, with true noncontrast (TNC) images as references and explored its dosimetric advantages compared to using TCE images.

Exploring G Protein-Coupled Receptors in Hematological Cancers.

Hematological cancers, such as lymphomas and leukemias, pose significant challenges in oncology, necessitating a deeper understanding of their molecular landscape to enhance therapeutic strategies. This article critically examines and discusses recent research on the roles of G protein-coupled receptors (GPCRs) in myeloma, lymphomas, and leukemias with a particular focus on pediatric acute lymphoblastic (lymphocytic) leukemia (ALL). By utilizing RNA sequencing (RNA-seq), we analyzed GPCR expression patterns in pediatric ALL samples (aged 3-12 years old), with a further focus on Class A orphan GPCRs.

Identifying Subsets of Cancer Patients with an Increased Risk of Developing Cutaneous Melanoma: A Surveillance, Epidemiology, and End Results-Based Analysis.

Cancer survivors have an increased risk of developing second primary malignancies. We aimed to identify whether certain cancers lead to an increased risk of developing melanoma among cancer survivors. We evaluated the risk of developing cutaneous melanoma after the 20 most common cancers in the United States through the Surveillance, Epidemiology, and End Results database.

PARP1 promotes tumor proliferation in lenalidomide-resistant multiple myeloma via the downregulation of microRNA-192-5p-AKT signaling.

Background: Lenalidomide-based therapies are recommended as first-line treatment for multiple myeloma (MM) patients, regardless of the transplant eligibility. Resistance to lenalidomide is a clinical problem that urgently needs to be addressed. The expression of poly(ADP-ribose) polymerase 1 (PARP1) is abnormally high in a variety of tumor tissues including MM.

The current socioeconomic and regulatory landscape of immune effector cell therapies.

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T cells to recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for a range of solid tumors.

The LILRB family in hematologic malignancies: prognostic associations, mechanistic considerations, and therapeutic implications.

The leukocyte immunoglobulin-like receptor B (LILRB) proteins, characterized by their transmembrane nature and canonical immunoreceptor tyrosine-based inhibitory motifs (ITIM) signaling, play a pivotal role in maintaining immune homeostasis and are implicated in the pathogenesis of various disease states. This comprehensive review will focus on the intricate involvement of the LILRB family in hematologic malignancies. These receptors have emerged as valuable diagnostic and prognostic biomarkers in leukemia, lymphoma, and myeloma.

Bortezomib induces Rho-dependent hyperpermeability of endothelial cells synergistically with inflammatory mediators.

Background: Bortezomib (BTZ), a selective 26 S proteasome inhibitor, is clinically useful in treating multiple myeloma and mantle cell lymphoma. BTZ exerts its antitumor effect by suppressing nuclear factor-B in myeloma cells, promoting endothelial cell apoptosis, and inhibiting angiogenesis. Despite its success, pulmonary complications, such as capillary leak syndrome of the vascular hyperpermeability type, were reported prior to its approval.

Molecular insights unlocking therapeutic potential for multiple myeloma and bone disease management.

Multiple myeloma (MM), a hematologic malignancy characterized by the clonal expansion of plasma cells within the bone marrow, is associated with severe health complications, including osteolytic bone lesions that significantly increase the risk of fractures, leading to higher morbidity and mortality rates. One intriguing protein in this context is the RNA polymerase binding factor Che-1/AATF (Che-1), which has emerged as a potential player in the survival and proliferation of myeloma cells. Hippo pathway has been shown to be an important mediator of oncogenesis in solid tumors, especially for its role in shaping a tumor microenvironment favorable to cancer maintenance and spread.

Bortezomib-releasing silica-collagen xerogels for local treatment of osteolytic bone- and minimal residual disease in multiple myeloma.

Background: Accumulation of malignant plasma cells in the bone marrow causes lytic bone lesions in 80% of multiple myeloma patients. Frequently fracturing, they are challenging to treat surgically. Myeloma cells surviving treatment in the presumably protective environment of bone lesions impede their healing by continued impact on bone turnover and can explain regular progression of patients without detectable minimal residual disease (MRD).

Evaluate the renal system damage caused by zoledronic acid: a comprehensive analysis of adverse events from FAERS.

Background: Zoledronic acid (ZA) is widely used for the treatment of osteolytic bone metastases in malignancies and osteoporosis, but it has been associated with renal impairment. In this study, we investigated adverse events (AEs) related to renal and urinary system diseases associated with ZA using the U. S.

The impact of high-risk cytogenetic abnormalities in extramedullary multiple myeloma in the era of novel agents: insights from a multicenter study.

Purpose: This study aimed to examine the impact of high-risk cytogenetic abnormalities (HRA) on the survival outcomes of multiple myeloma patients with extramedullary disease (EMD) in the era of novel agents, utilizing the largest dataset of extramedullary multiple myeloma patients in China.

Methods: This study included a total of 371 patients with EMD, comprising 113 patients with de novo EME and 258 patients with EMB.

Results: Patients with one HRA and those with ≥ 2 HRA demonstrated significantly worse overall survival (OS) (P < 0.

Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3.

Multiple myeloma (MM) is the second common hematological malignancy characterized by the abnormal proliferation of plasma cells. Although advances in the past decades have led to improved outcomes and longer survival, MM remains largely incurable. New targets and targeted therapy may help to achieve better outcomes.

The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study.

Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications.

Effects of Socioeconomic Status and Healthcare Resource Availability on Survival in Older (≥66 years) Non-Hispanic Black Patients Versus Non-Hispanic White Patients With Multiple Myeloma.

Background: Several factors contribute to the known disparities in overall survival (OS) between non-Hispanic Black (NHB) patients and non-Hispanic White (NHW) patients with multiple myeloma (MM).

Patients And Methods: To explore whether socioeconomic status (SES) and healthcare resource (HCR) availability impacts OS, this retrospective study used linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims and Area Health Resource Files to identify NHB and NHW patients aged ≥66 years with MM (newly diagnosed 6/1/2013-12/31/2017). Continuous Medicare A and B enrollment until 12/31/2019 or preceding death was required.

The inhibitory receptor PVRIG is dominantly expressed in the bone marrow of patients with multiple myeloma and its blockade enhances T-cell engager's immune activation.

Therapeutic advances in treating patients with multiple myeloma (MM), including novel immunotherapies, have improved the disease control, but it remains incurable. Although traditional immune check point inhibitors have shown limited clinical benefit, targeting alternative immune-inhibitory pathways may offer a novel way to address relapsed disease. Blockade of the immune regulator TIGIT was shown to enhance antitumor immunity in preclinical MM models.