multiple myeloma
multiple myeloma
Overview
Multiple myeloma is a malignant plasma cell disorder characterized by clonal expansion of abnormal plasma cells in the bone marrow, excessive immunoglobulin production, and progressive disruption of normal hematopoiesis and skeletal integrity. It is a heterogeneous hematologic cancer with a relapsing course, and despite major therapeutic advances, it remains generally incurable because of clonal evolution, drug resistance, and supportive interactions within the bone marrow tumor microenvironment.
Biologically, multiple myeloma is shaped by interactions among malignant plasma cells, stromal cells, macrophages, and proinflammatory cytokines, with frequent dependence on pathways involving proteasome function, nuclear export, epigenetic regulation, and immune evasion. Recent research has also highlighted targets such as BCMA, CD38, XPO1, PSMD1, CBP/p300, syndecan-1, and other core dependencies, reflecting the shift toward immunotherapy, targeted therapy, and biomarker-guided treatment. The disease is also associated with complications including frailty after autologous stem cell transplantation, infection risk, bone disease, renal impairment, and rare central nervous system involvement.
Focus of Latest Publications
Recent publications on multiple myeloma have focused on improving trial follow-up, refining risk stratification, and identifying therapeutic targets. One protocol describes the Blood Cancer Clinical Trials Long-term Follow-up Using Integrated Healthcare Systems platform, which will link multiple myeloma clinical trial data with routinely collected healthcare systems data to support extended follow-up and additional methodological and clinical research. This work is aimed at evaluating whether healthcare systems data can provide outcomes at a standard equivalent to trial-specific follow-up while reducing cost, time, and resource burden.
Several studies addressed treatment-related care in multiple myeloma, particularly in the context of novel immunotherapies and special populations. The CLARITY study protocol will generate real-world, longitudinal infection data in patients with lymphoma and myeloma receiving chimeric antigen receptor T-cell therapy and bispecific antibody therapy, with the goal of characterizing infection timing, including late events, and informing risk prediction. Another expert opinion paper discusses diagnostic and treatment options for hematologic malignancies during pregnancy, including multiple myeloma, and considers chemotherapy, radiation therapy, and immunotherapy in this setting. A separate study on lymphocyte collection in B-cell lymphoma and myeloma emphasizes that early lymphocyte collection, ideally before extensive chemotherapy, may improve T-cell quality for future CAR T-cell therapy.
Other recent work has focused on disease progression and trial design in myeloma-related conditions. In solitary bone plasmacytoma with minimal marrow involvement, a multicenter study found a high risk of progression to multiple myeloma after radiation therapy, with earlier progression and shorter time to progression in patients with minimal marrow involvement than in those with solitary bone plasmacytoma alone. Del(17p) and 1q+ were associated with shorter time to progression in the minimal marrow involvement group, and the authors suggested that these findings support prospective studies incorporating frontline systemic therapy for this high-risk population. In parallel, a review of phase 3 randomized controlled trials in hematologic malignancies found that renal impairment was frequently used as an exclusion criterion, including in multiple myeloma trials, often based on creatinine clearance or estimated glomerular filtration rate, raising concerns about generalizability to patients with renal dysfunction.
Finally, human genetics studies have identified candidate targets relevant to multiple myeloma biology. A proteome-wide Mendelian randomization analysis of circulating proteins across B-cell malignancies identified protein-disease associations in multiple myeloma, including TNFSF13 (APRIL) and TNFRS13B (TACI), and integrated single-cell RNA sequencing, Bayesian colocalization, and clinical trial evidence to prioritize candidate drug targets. Together, these publications highlight ongoing efforts to improve long-term data capture, manage complications of advanced therapies, understand progression risk, and expand the therapeutic landscape in multiple myeloma.