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.

Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.

We previously demonstrated that reduced intrinsic electron transport chain (ETC) activity predicts and promotes sensitivity to the BCL-2 antagonist, venetoclax (Ven) in multiple myeloma (MM). Heme, an iron-containing prosthetic group, and metabolite is fundamental to maintaining ETC activity. Interrogation of the CD2 subgroup of MM from the CoMMpass trial (NCT01454297), which can be used as a proxy for Ven-sensitive MM (VS MM), shows reduced expression of the conserved heme biosynthesis pathway gene signature.

Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

Cumulative Deficits Frailty Index and Relationship Status Predict Survival in Multiple Myeloma.

Several tools have been proposed for assessing frailty in multiple myeloma (MM), but most are based on clinical trial datasets. There is also limited data on the association between frailty and patient-reported outcomes, and the prognostic value of social determinants of health. This study evaluates the prognostic impact of frailty, based on the cumulative deficit frailty index (FI), and relationship and socioeconomic status (SES) in newly diagnosed MM patients.

Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.

Immune surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a previously unknown function for intracellular C3d, we found that C3d engaged T cell responses against malignant PC in the bone marrow of mice that had developed multiple myeloma spontaneously.

Efficacy of chimeric antigen receptor engineered natural killer cells in the treatment of hematologic malignancies: a systematic review and meta-analysis of preclinical studies.

Background: Chimeric antigen receptor (CAR) engineered NK cells (CAR-NK) are a novel approach to the immunotherapy of hematologic malignancies which seeks to overcome some of the challenges faced by CAR-T cells (CAR-T). With few published clinical studies, preclinical studies can identify strategies to accelerate clinical translation. We conducted a systematic review on the preclinical in vivo use of CAR-NK for the treatment of hematologic malignancies to assess these therapies in a holistic and unbiased manner.

Recurrent Cardiac Tamponade from Multiple Myeloma While Receiving Teclistamab.

Bispecific therapy has changed the treatment paradigm for multiple myeloma. We report a patient with recurrent malignant pericardial effusions with cardiac tamponade and new atrial fibrillation during treatment, suggesting that new or worsening pericardial disease may be a potential cardiovascular adverse effect of bispecific therapy.

Correction to: Searching for Immunocompromising Conditions in Low-risk Adults After Invasive Pneumococcal Disease: An Opportunity to Uncover Multiple Myeloma Early.

[This corrects the article DOI: 10.1093/ofid/ofae653.].

Dosing strategy of intrapleural bortezomib for myelomatous pleural effusion: A case report and review of literature.

Myelomatous pleural effusion (MPE) is a rare, often treatment-resistant complication of multiple myeloma. Intrapleural bortezomib shows promise but lacks standardized dosing. We report a 62-year-old woman with MPE treated with 1.

Rapid high-dose cyclophosphamide as bridging treatment for advanced therapies in multiple myeloma.

Patients with relapsed/refractory multiple myeloma proceeding with chimeric antigen receptor (CAR) T-cell therapy or bispecific antibodies (BsAb) may need bridging therapy to realize their benefits. We evaluated the efficacy and safety of rapid, peripheral, high-dose cyclophosphamide (TurboCy) in 15 patients intending to proceed with CAR T-cell therapy, BsAbs, or long-term regimens. The overall response rate was 80% and the clinical benefit rate was 100% in a heavily pretreated high-risk cohort.

Immediate improvement in patient care: Auditing adherence to the British Society for Haematology guidelines on screening and management of the long-term consequences of multiple myeloma and treatment.

Advances in myeloma have resulted in improved prognosis for patients. However complications of the disease and treatment, pose a risk of specific long-term consequences. An audit tool was adapted to assess adherence to the British Society for Haematology guidelines for screening and management of long-term myeloma consequences.

The evolving treatment landscape of multiple myeloma in Portugal: A nation-wide retrospective cohort study of real-world clinical practice.

Objectives: To characterize variations in real-world treatment patterns in multiple myeloma (MM) in Portugal over a 5-year period.

Methods: A retrospective cohort multicenter study using secondary data of national hospital drug consumption database from 11 Portuguese public hospitals between 2017 and 2022.

Results: Number of MM-treated patients increased 53% over 5 years (from 825 to 1266 patients).