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Hematology (Amsterdam, Netherlands) Dec 2022Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens after inductive therapy are still controversial and opaque.
OBJECTIVE
We aimed to identify the most effective maintenance treatment for newly diagnosed multiple myeloma (NDMM) patients via network meta-analysis.
METHOD
We searched PubMed, Embase, Cochrane Library, Scopus, and Google Scholars from inception to April, 2022. Odds ratios (ORs) were generated for dichotomous variants. The primary endpoint was overall survival (OS).
RESULTS
Eventually a total of 19 trials, including 11 treatments and 8337 patients, were included in this analysis. For OS, lenalidomide (OR ranged from 1.61 to 1.99) and daratumumab (OR ranged from 1.83 to 2.41) showed significant efficacy over placebo. Maintenance therapy comprising lenalidomide-carfilzomib (OR ranged from 3.19 to 6.95), lenalidomide-prednisone (OR ranged from 2.62 to 4.44), bortezomib-thalidomide (OR ranged from 2.48 to 3.64), daratumumab (OR ranged from 2.0 to 2.98), lenalidomide (OR ranged from 1.4 to 3.19), ixazomib (OR ranged from 1.36 to 2.05), thalidomide (OR ranged from 1.5 to 1.86) demonstrated significant effects in prolongin PFS compared with placebo; Among the efficient therapies, lenalidomide-carfilzomib was significantly superior to lenalidomide (OR ranged from 2.18 to 2.20), daratumumab (OR ranged from 1.49 to 2.66) and ixazomib (OR ranged from 2.75 to 3.57).
CONCLUSION
Considering OS and PFS, lenalidomide-carfilzomib should be recommended as the best therapy. In clinical practice, this must be weighed against the increased risk of adverse events and financial burden. However, more head-to-head studies are needed to confirm these findings.
Topics: Antineoplastic Combined Chemotherapy Protocols; Boron Compounds; Bortezomib; Glycine; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Prednisone; Thalidomide
PubMed: 36125238
DOI: 10.1080/16078454.2022.2121900 -
Atherosclerosis Plus Dec 2023To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM).
BACKGROUND AND AIMS
To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM).
METHODS
We searched PubMed and Cochrane library databases (up to 20 September 2022) for studies with evidence on HDL-C in patients with MM. A qualitative synthesis of published prospective and retrospective studies for the role of HDL-C and other lipid profile parameters in MM was performed. Additionally, a meta-analysis on HDL-C mean differences (MD) between MM cases and controls was performed.
RESULTS
Fourteen studies (3 prospective, 11 retrospective) including 895 MM patients were eligible for this systematic review. Ten studies compared HDL-C levels in MM patients with healthy controls. In these 10 studies (n = 17,213), pooled analyses showed that MM patients had significantly lower HDL-C levels compared to healthy controls (MD: -13.07 mg/dl, 95% CI: -17.83, -8.32, p < 0.00001). Regarding secondary endpoints, total cholesterol (TC) (MD: -22.19 mg/dl, 95% CI: -39.08, -5.30) and apolipoprotein A-I (apoA-I) (-40.20 mg/dl, 95% CI: -55.00, -25.39) demonstrated significant decreases, while differences in low-density lipoprotein cholesterol (LDL-C) (MD: -11.33 mg/dl, 95% CI: -36.95, 14.30) and triglycerides (MD: 9.93 mg/dl, 95% CI: -3.40, 23.26) were not shown to be significant.
CONCLUSIONS
HDL-C, as well as TC and apoA-I, levels are significantly decreased in MM. Hence, lipid profile parameters should be taken into account when assessing such patients.
PubMed: 37780686
DOI: 10.1016/j.athplu.2023.09.003 -
Hematology (Amsterdam, Netherlands) Dec 2023Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory multiple myeloma (RRMM), whereas its optimal timing and drug combination remain unclear. In order to assess the various regimens that incorporate selinexor, a systematic review and meta-analysis was conducted.
METHODS
Clinical trials and real-world studies involving MM patients treated with selinexor were included. Pooled risk ratio (RR) was calculated to compare the rates, along with a 95% confidence interval (CI) and concurrent -value assessment. A random-effects model was employed to provide a more conservative evaluation.
RESULTS
A total of 16 studies enrolling 817 patients were reviewed. The usage of selinexor as the fifth-line or prior therapy achieved a higher objective response rate (ORR) (65.9% versus 23.4%, < 0.01) and longer pooled progression-free survival (PFS) (median: 12.5 months versus 2.9 months, < 0.01) than those after the fifth-line usage. In addition, early usage also resulted in a consistent trend of pooled overall survival (median: 22.7 months versus 8.9 months, = 0.26), compared with post-fifth-line usage. Selinexor and dexamethasone (Xd) plus either protease inhibitors (PIs) or immunomodulatory drugs (IMiDs) achieved better ORRs than the Xd-only regimen for RRMM, with ORRs of 56.1%, 52.5% and 24.6%, respectively (< 0.01).
CONCLUSION
In conclusion, using selinexor as the fifth-line or prior therapy had a beneficial impact on RRMM. The regimen of Xd plus PIs or IMiDs was recommended.
Topics: Humans; Multiple Myeloma; Immunomodulating Agents; Dexamethasone; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36920065
DOI: 10.1080/16078454.2023.2187972 -
International Journal of Oncology Jan 2018Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between... (Review)
Review
Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using PubMed. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma, prostate cancer and urothelial carcinoma were evaluated. Annexin A2 expression correlates with resistance to treatment, binding to the bone marrow, histological grade and type, TNM-stage and shortened overall survival. The regulation of Annexin A2 is of interest due to its potential as target for a more individualized cancer management.
Topics: Animals; Annexin A2; Biomarkers, Tumor; Humans; Neoplasms
PubMed: 29115416
DOI: 10.3892/ijo.2017.4197 -
ClinicoEconomics and Outcomes Research... 2016To review published cost-effectiveness analyses (CEA) assessing bortezomib (BTZ) for multiple myeloma (MM) and explore possible bias affecting the cost-effectiveness of... (Review)
Review
OBJECTIVES
To review published cost-effectiveness analyses (CEA) assessing bortezomib (BTZ) for multiple myeloma (MM) and explore possible bias affecting the cost-effectiveness of BTZ.
METHODS
Literature was searched for published CEAs assessing BTZ or BTZ-containing regimens for MM from 2003 to 2015. The reported incremental cost-effectiveness ratios (ICER) were adjusted by 2014 country-specific gross domestic product per capita (GDPPC) to compare the cost-effectiveness threshold of the World Health Organization (3 GDPPC per gained quality-adjusted life year [QALY]).
RESULTS
A total of 17 published CEAs were included in this review. When compared to non-BTZ treatments, BTZ-containing regimens were cost-effective for induction treatment prior to stem cell transplantation (SCT) in Canada, Poland, and Germany (ICER per QALY: 0.9299-2.254 GDPPC). BTZ/melphalan/prednisolone (VMP) was cost-effective for previously untreated and SCT-ineligible MM patients when compared to melphalan plus prednisolone (MP), melphalan/prednisone/lenalidomide with lenalidomide maintenance, and cyclophosphamide/thalidomide/dexamethasone (CTD) (ICER per QALY: dominant to 2.374 GDPPC) in Canada, UK, and USA. BTZ was cost-effective for relapsed/refractory MM when compared to best supportive care (ICER per life year: 0.9317-1.8210 GDPPC) in the UK and the USA, thalidomide in USA (0.5178 GDPPC/LY), and dexamethasone (DEX) in four Nordic countries (€54,451-€81,560/QALY). However, the cost-effectiveness for VMP versus MP plus thalidomide (MPT) and continuous lenalidomide (LEN) plus low-dose DEX (RD) for previously untreated and SCT-ineligible MM patients and BTZ versus LEN/DEX for relapsed/refractory MM patients could be unreliable because of the bias associated with model design and the indirect comparisons of treatment effects.
CONCLUSION
Published CEAs suggested that BTZ or BTZ-containing regimens were cost-effective when compared to most non-BTZ treatments for MM. However, the conflicting cost-effectiveness for VMP versus MPT for previously untreated and SCT-ineligible MM and BTZ versus LEN/DEX for relapsed/refractory MM needs more robust evidence for further clarification.
PubMed: 27217786
DOI: 10.2147/CEOR.S104195 -
Current Oncology (Toronto, Ont.) May 2023Multiple myeloma usually affects older adults. However, younger patients constitute a significant subset as approximately 10% of cases occur in subjects younger than 50... (Review)
Review
Multiple myeloma usually affects older adults. However, younger patients constitute a significant subset as approximately 10% of cases occur in subjects younger than 50 years old. Young patients, who are underrepresented in the literature, are diagnosed during their most productive years of life, urging the need for tailored treatment approaches. This literature review aims to report recent studies specifically addressing young patients with a focus on characteristics at diagnosis, cytogenetics, treatments, and outcomes. We searched PubMed for studies involving young patients with multiple myeloma ≤50 years old. The time span of our literature review search was from 1 January 2010 to 31 December 2022. Overall, 16 retrospective studies were analyzed for this review. Young patients with multiple myeloma tend to have less advanced disease, more frequent light chain subtypes, and survive longer compared to their older counterparts. However, available studies included a limited number of patients; the newest revised international staging system was not used to stratify patients, cytogenetics varied from one cohort to another, and most patients did not receive contemporary triplet/quadruplet treatments. This review emphasizes the need to perform contemporary, large-scale retrospective studies to improve knowledge regarding the presentation and outcomes of young myeloma patients in the era of modern treatments.
Topics: Humans; Aged; Middle Aged; Multiple Myeloma; Retrospective Studies
PubMed: 37366879
DOI: 10.3390/curroncol30060396 -
Expert Opinion on Investigational Drugs Jun 2016Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor... (Review)
Review
INTRODUCTION
Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM.
AREAS COVERED
In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed.
EXPERT OPINION
Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cell Proliferation; Humans; Lenalidomide; Multiple Myeloma; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Sorafenib; Thalidomide
PubMed: 26998658
DOI: 10.1517/13543784.2016.1169272 -
Journal of Musculoskeletal & Neuronal... Dec 2022Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM)... (Meta-Analysis)
Meta-Analysis Review
Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.
Topics: Humans; Diphosphonates; Multiple Myeloma; Denosumab; Zoledronic Acid; Clodronic Acid
PubMed: 36458395
DOI: No ID Found -
Critical Reviews in Oncology/hematology Mar 2021This study aims to evaluate the efficacy and safety of Daratumumab-based induction therapy (DBI) in newly diagnosed multiple myeloma (MM). We identified four eligible... (Meta-Analysis)
Meta-Analysis Review
This study aims to evaluate the efficacy and safety of Daratumumab-based induction therapy (DBI) in newly diagnosed multiple myeloma (MM). We identified four eligible RCTs including 2735 patients. The primary outcomes of RCTs involving transplant eligible (TEMM) and non-transplant eligible MM (NTEMM) were stringent complete response (sCR) and progression-free survival (PFS) respectively. Meta-analysis was performed using random-effects models. DBI improved sCR rates for standard risk (SR) (OR 1.86, 95 % CI 1.41-2.46) but not HiR (high risk) (OR 0.78, 95 % CI 0.41-1.48) (interaction P = 0.01) TEMM. In NTEMM, DBI improved PFS in SR (HR 0.44, 95 % CI 0.35-0.55) but not HiR patients. (HR 0.81, 95 % CI 0.52-1.27) (interaction P = 0.02). In conclusion, while DBI is efficacious in SR patients, there is insufficient data to support a benefit in HiR-MM.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans; Induction Chemotherapy; Multiple Myeloma
PubMed: 33387628
DOI: 10.1016/j.critrevonc.2020.103211 -
Diagnostics (Basel, Switzerland) Jun 2023Multiple myeloma (MM) is one of the most common hematological malignancies affecting the bone marrow. Radiomics analysis has been employed in the literature in an... (Review)
Review
Multiple myeloma (MM) is one of the most common hematological malignancies affecting the bone marrow. Radiomics analysis has been employed in the literature in an attempt to evaluate the bone marrow of MM patients. This manuscript aimed to systematically review radiomics research on MM while employing a radiomics quality score (RQS) to accurately assess research quality in the field. A systematic search was performed on Web of Science, PubMed, and Scopus. The selected manuscripts were evaluated (data extraction and RQS scoring) by three independent readers (R1, R2, and R3) with experience in radiomics analysis. A total of 23 studies with 2682 patients were included, and the median RQS was 10 for R1 (IQR 5.5-12) and R3 (IQR 8.3-12) and 11 (IQR 7.5-12.5) for R2. RQS was not significantly correlated with any of the assessed bibliometric data (impact factor, quartile, year of publication, and imaging modality) ( > 0.05). Our results demonstrated the low quality of published radiomics research in MM, similarly to other fields of radiomics research, highlighting the need to tighten publication standards.
PubMed: 37370916
DOI: 10.3390/diagnostics13122021