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Haematologica Jun 2024Not available.
Not available.
PubMed: 38867588
DOI: 10.3324/haematol.2024.285368 -
Clinical and Experimental Medicine Jun 2024Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking.
PURPOSE
Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking.
METHODS
This retrospective case-control study utilized the Korean National Health Insurance Service database (2009-2020) to compare the incidence of cardiovascular disease (CVD) between patients with MM and a matched control group, focusing on long-term (> 5 years) survivors. A preliminary case cohort (n = 15,402 patients with MM) and a matched control cohort (n = 123,216 patients without MM) were established based on birth year and sex. Following 1:1 propensity score matching, the final matched cohorts each comprised 15,402 participants.
RESULTS
The case and control cohorts were comparable in mean age (66.2 ± 11.5 years vs. 66.1 ± 11.3 years), sex, age distribution, and comorbidities. By the 8-year follow-up, the cumulative incidence of CV events (12.5% vs. 22.1%) and CVD risk were significantly lower in the case cohort. The 5-year landmark analysis revealed significant differences in CVD incidence between the cohorts (7.8% [case cohort] vs. 9.8% [control cohort]), with variations across age groups and sex, highlighting a significantly higher CVD risk among patients aged < 50 years in the case cohort (P < 0.001).
CONCLUSIONS
These findings underscore the need for vigilant CVD monitoring in MM long-term survivors, particularly those aged < 50 years at first diagnosis.
IMPLICATION FOR CANCER SURVIVORS
This study highlights the importance of integrating cardiovascular monitoring and risk management into long-term care for MM survivors, with a focus on younger patients and personalized interventions.
Topics: Humans; Multiple Myeloma; Male; Female; Aged; Middle Aged; Republic of Korea; Case-Control Studies; Cardiovascular Diseases; Retrospective Studies; Incidence; Cancer Survivors; Aged, 80 and over; Risk Factors; Adult
PubMed: 38864999
DOI: 10.1007/s10238-024-01368-2 -
Cancer Medicine Jun 2024Promising outcomes have been observed in multiple myeloma (MM) with the use of immunotherapies, specifically chimeric antigen receptor T (CAR-T) cell therapy. However, a...
BACKGROUND
Promising outcomes have been observed in multiple myeloma (MM) with the use of immunotherapies, specifically chimeric antigen receptor T (CAR-T) cell therapy. However, a portion of MM patients do not respond to CAR-T therapy, and the reasons for this lack of response remain unclear. The objective of this study was to investigate the impact of miR-34a on the immunosuppressive polarization of macrophages obtained from MM patients.
METHODS
The levels of miR-34a and TLR9 (Toll-like receptor 9) were examined in macrophages obtained from both healthy individuals and patients with MM. ELISA was employed to investigate the cytokine profiles of the macrophage samples. Co-culture experiments were conducted to evaluate the immunomodulatory impact of MM-associated macrophages on CAR-T cells.
RESULTS
There was an observed suppressed activation of macrophages and CD4 T lymphocytes in the blood samples of MM patients. Overexpression of miR-34a in MM-associated macrophages dampened the TLR9 expression and impaired the inflammatory polarization. In both the co-culture system and an animal model, MM-associated macrophages suppressed the activity and tumoricidal effect of CAR-T cells in a miR-34a-dependent manner.
CONCLUSION
The findings imply that targeting the macrophage miR-34a/TLR9 axis could potentially alleviate the immunosuppression associated with CAR-T therapy in MM patients.
Topics: Multiple Myeloma; MicroRNAs; Toll-Like Receptor 9; Humans; Animals; Mice; Signal Transduction; Coculture Techniques; Tumor-Associated Macrophages; Macrophages; Immunotherapy, Adoptive; Male; Female; Macrophage Activation; Cell Line, Tumor
PubMed: 38864479
DOI: 10.1002/cam4.7387 -
OTO Open 2024
PubMed: 38863484
DOI: 10.1002/oto2.144 -
Cell Communication and Signaling : CCS Jun 2024Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable... (Review)
Review
Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.
Topics: Humans; Multiple Myeloma; TOR Serine-Threonine Kinases; Signal Transduction; Animals; Molecular Targeted Therapy; MTOR Inhibitors; Mechanistic Target of Rapamycin Complex 2
PubMed: 38862983
DOI: 10.1186/s12964-024-01699-3 -
Blood Cancer Journal Jun 2024
Topics: Humans; Multiple Myeloma; Neoplasm Staging; Female; Male; Middle Aged; Aged; Adult; Aged, 80 and over; Cohort Studies
PubMed: 38862493
DOI: 10.1038/s41408-024-01076-w -
Kansas Journal of Medicine 2024
PubMed: 38859988
DOI: 10.17161/kjm.vol17.21630 -
Journal of Korean Medical Science Jun 2024Multiple myeloma (MM) patients are at risk of skeletal-related events (SREs) like spinal cord compression, pathologic fractures, bone surgery, and radiation to bone....
BACKGROUND
Multiple myeloma (MM) patients are at risk of skeletal-related events (SREs) like spinal cord compression, pathologic fractures, bone surgery, and radiation to bone. Real-world data regarding SREs in MM are limited.
METHODS
We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service (HIRA) database from 2007 to 2018.
RESULTS
Over a 12-year study period, we identified 6,717 patients who developed symptomatic MM. After a median follow-up of 35.1 months (interquartile range [IQR], 20.8-58.2 months), 43.6% of these patients experienced SREs, and 39.6% had four or more SREs. One in five patients (20.0%) experienced pathologic fractures within the first year of follow-up. The median time to first SRE was 9.6 months (IQR, 1.2-25.8 months), with 3.0 months in the group with prior SREs and 19.8 months in the group without prior SREs. During follow-up, 78.5% of patients received bisphosphonates. Multiple logistic regression analysis revealed several factors associated with an increased risk of SREs, including being female (odds ratio [OR], 1.44), aged 50 or older (OR, 1.87), having cerebrovascular disease (OR, 1.34), undergoing first-line chemotherapy regimens not containing bortezomib or lenalidomide (OR, 1.49), and being in the group with prior SREs and bisphosphonate use (OR, 5.63), compared to the group without prior SREs and without bisphosphonate use.
CONCLUSION
This population-based study is the first to report the incidence and risk factors of SREs in Korean MM patients, which can be used to assess their bone health.
Topics: Humans; Multiple Myeloma; Female; Male; Retrospective Studies; Middle Aged; Aged; Diphosphonates; Risk Factors; Databases, Factual; Republic of Korea; Bone Density Conservation Agents; Odds Ratio; Fractures, Spontaneous; Spinal Cord Compression; Adult; Logistic Models
PubMed: 38859738
DOI: 10.3346/jkms.2024.39.e175 -
Chinese Clinical Oncology May 2024Hematological malignancies (HMs) are a group of neoplasms with hematopoietic origin, currently divided into leukemias, lymphomas and multiple myeloma (MM). Although the...
BACKGROUND AND OBJECTIVE
Hematological malignancies (HMs) are a group of neoplasms with hematopoietic origin, currently divided into leukemias, lymphomas and multiple myeloma (MM). Although the advances in the management of HMs, the rate of drug resistance, relapse and refractory disease has been increasing, requiring new therapeutic strategies. In this review, we aim to summarize metformin's antitumoral mechanisms of action and present the latest studies of metformin action in HMs, including in resistant ones.
METHODS
For this review of literature, studies published between 1996 and 2023 from PubMed and clinical trials submitted to clinicaltrials.gov were considered.
KEY CONTENT AND FINDINGS
Throughout this review we demonstrated the capacity of metformin to act as an anti-HMs drug, being able to re-sensitize HMs to classical anti-HMs agents and to overcome relapse and refractory HMs, as shown in vitro and in vivo studies. Associated with the potential anti-HM effect of metformin, some clinical trials are in progress, including in the view of reducing resistance and recurrence rate of HMs, which requires further exploration. The relationship among HMs cancer stem cells (HMs CSCs), drug resistance, cancer recurrence, and the effect of metformin in inhibiting CSCs were also discussed, despite this field needing more attention.
CONCLUSIONS
In summary, metformin is a promising anti-HMs drug that can enhance patients' survival and prognosis through its action in the improvement of HMs response.
PubMed: 38859606
DOI: 10.21037/cco-23-157