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EClinicalMedicine Apr 2023Biomarker-defined patients with smoldering multiple myeloma (SMM) were included in the diagnostic category of multiple myeloma (MM) by the International Myeloma Working...
SLiM CRAB criteria revisited: temporal trends in prognosis of patients with smoldering multiple myeloma who meet the definition of 'biomarker-defined early multiple myeloma'-a systematic review with meta-analysis.
BACKGROUND
Biomarker-defined patients with smoldering multiple myeloma (SMM) were included in the diagnostic category of multiple myeloma (MM) by the International Myeloma Working Group (IMWG) in 2014. This includes ≥60% bone marrow plasma cells (BMPCs), free light chain ratio (FLCratio) ≥100, and >1 MRI-defined ≥5 mm focal lesion, also called SLiM CRAB MM. We examined whether the risk of progression of SLiM CRAB MM patients to CRAB positive MM described in recent studies differs from that reported in earlier studies published before the introduction of the new diagnostic criteria.
METHODS
We conducted a systematic review with meta-analysis, and included studies on Embase and PubMed (01/01/2010-01/11/2022), selecting studies with digitizable progression curves. Inconsistent studies were excluded. We created forest plots using random effects models from digitized and published data and Kaplan-Meier curves. Main outcomes were median time to progression (TTP), 2-year progression risk, and odds ratios (ORs) comparing 2-year progression risks.
FINDINGS
Our meta-analysis including 11 studies with 3482 patients found an approximately 3-fold longer TTP and 50% lower 2-year progression risk of SliM CRAB MM patients in recent (published after 2014) compared with earlier studies. Median TTP in patients with ≥60% BMPCs was 30.31 months [18.71-62.93] in recent compared with 9.20 months [6.02-15.56] in earlier studies; the 2-year progression risk was 45.45% [20.12-62.75] compared with 86.21% [65.74-94.45] in the respective time periods. In patients with a FLCratio ≥ 100, the median TTP was 48.06 months [40.51-64.91] vs. 15.33 months [9.38-19.10], and the 2-year progression risk was 31.61% [25.30-37.39] vs. 73.00% [62.39-80.62] in recent and earlier studies, respectively. Tests for heterogeneity showed that the two time periods differed significantly in their ORs when comparing patients who met the high-and low risk criteria. No appropriate recent studies on focal lesions have been published.
INTERPRETATION
Recent studies show significantly improved prognosis of biomarker-defined MM with ≥60% BMPCs and FLCratio ≥ 100. This warrants careful evaluation for signs of progression before treatment initiation.
FUNDING
Funding was provided by the Austrian Forum against Cancer.
PubMed: 36969337
DOI: 10.1016/j.eclinm.2023.101910 -
Autoimmunity Reviews May 2022Patients with primary Sjögren's syndrome(pSS) have increased risk of non-Hodgkin lymphoma (NHL). However, whether pSS patients have increased risk of other malignancies... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Patients with primary Sjögren's syndrome(pSS) have increased risk of non-Hodgkin lymphoma (NHL). However, whether pSS patients have increased risk of other malignancies is unclear. The aim of this study is to investigate the association between pSS and the risk of malignancy, with a focus on hematological malignancies besides lymphoma and solid tumors through a systematic review and meta-analysis.
METHOD
We searched PubMed and EMBASE by March 21st 2021. Inclusion criteria were as follows: (1) pSS was the exposure of interest; (2) newly developed malignancies were the outcome of interest; (3) standardized incidence ratio or relative risk with 95% confidence interval or essential data to calculate them were reported. (4) Study design was cohort study. Patient with other connective diseases were excluded. Quality assessment was conducted according to Newcastle-Ottawa Scale for cohort study. Random or fixed effect models were used to calculate the pooled SIR according to heterogeneity measured by I.
RESULTS
A total of 1003 articles were found by a comprehensive search in PubMed and EMBASE. Twenty-eight articles were eligible. Four of them were from the same database, and the one with longest observational span was chosen. Therefore, twenty-five articles were included for final analysis, which involved more than 47,607 pSS patients with the follow-up of more than 452,468 person-year. We found that pSS was significantly associated with increased risks of overall malignancy(pooled SIR 2.17, 95%1.57-3.00), hematological malignancy(pooled SIR 11.55, 95%CI 4.32-30.90) including NHL(pooled SIR 13.71, 95%CI 8.83-21.29), Hodgkin lymphoma(pooled SIR 8.84, 95%CI 5.00-15.61), multiple myeloma(pooled SIR 8.27, 95%CI 3.08-22.24), leukemia(pooled SIR 2.56, 95%CI 1.78-3.69) and solid tumors(pooled SIR 1.39, 95%CI 0.90-2.13) including lung cancer(pooled SIR 1.55, 95%CI 1.29-1.85), thyroid cancer(pooled SIR 2.05, 95%CI 1.20-3.48), non-melanoma skin cancer(pooled SIR 1.71, 95%CI 1.08-2.72), kidney/urinary tract cancer(pooled SIR 1.36, 95%CI 1.02; 1.81), liver cancer(pooled SIR 1.70, 95%CI 1.13-2.57) and prostate cancer(pooled SIR 1.50, 95%CI 1.02-2.22).
CONCLUSION
This meta-analysis showed that pSS patients had increased risk of overall cancer, which not only contributed by NHL, but also by other hematological malignancies and solid tumors.
Topics: Cohort Studies; Hematologic Neoplasms; Humans; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Risk Factors; Sjogren's Syndrome
PubMed: 35341972
DOI: 10.1016/j.autrev.2022.103084 -
Pharmacological Research Apr 2023Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell... (Meta-Analysis)
Meta-Analysis Review
Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.
Topics: Humans; Adult; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Chronic Disease; Multiple Myeloma; Recurrence; Cell- and Tissue-Based Therapy
PubMed: 36963592
DOI: 10.1016/j.phrs.2023.106742 -
Blood Advances Dec 2020The prognostic value of minimal residual disease (MRD) for progression-free survival (PFS) and overall survival (OS) was evaluated in a large cohort of patients with... (Meta-Analysis)
Meta-Analysis
The prognostic value of minimal residual disease (MRD) for progression-free survival (PFS) and overall survival (OS) was evaluated in a large cohort of patients with multiple myeloma (MM) using a systematic literature review and meta-analysis. Medline and EMBASE databases were searched for articles published up to 8 June 2019, with no date limit on the indexed database. Clinical end points stratified by MRD status (positive or negative) were extracted, including hazard ratios (HRs) on PFS and OS, P values, and confidence intervals (CIs). HRs were estimated based on reconstructed patient-level data from published Kaplan-Meier curves. Forty-four eligible studies with PFS data from 8098 patients, and 23 studies with OS data from 4297 patients were identified to assess the association between MRD status and survival outcomes. Compared with MRD positivity, achieving MRD negativity improved PFS (HR, 0.33; 95% CI, 0.29-0.37; P < .001) and OS (HR, 0.45; 95% CI, 0.39-0.51; P < .001). MRD negativity was associated with significantly improved survival outcomes regardless of disease setting (newly diagnosed or relapsed/refractory MM), MRD sensitivity thresholds, cytogenetic risk, method of MRD assessment, depth of clinical response at the time of MRD measurement, and MRD assessment premaintenance and 12 months after start of maintenance therapy. The strong prognostic value of MRD negativity and its association with favorable outcomes in various disease and treatment settings sets the stage to adopt MRD as a treatment end point, including development of therapeutic strategies. This large meta-analysis confirms the utility of MRD as a relevant surrogate for PFS and OS in MM.
Topics: Cytogenetics; Humans; Multiple Myeloma; Neoplasm, Residual; Prognosis; Treatment Outcome
PubMed: 33284948
DOI: 10.1182/bloodadvances.2020002827 -
Journal of Cancer Survivorship :... Apr 2023The purpose of this systematic review with meta-analysis was to evaluate the safety, feasibility and effectiveness of exercise in the palliative care phase for people... (Meta-Analysis)
Meta-Analysis
PURPOSE
The purpose of this systematic review with meta-analysis was to evaluate the safety, feasibility and effectiveness of exercise in the palliative care phase for people with advanced cancer.
METHODS
Electronic databases were searched for exercise randomised controlled trials involving individuals with incurable cancer that were published prior to April 14, 2021. Meta-analyses were performed to evaluate the effects of exercise on health outcomes. Subgroup effects for exercise mode, supervision, intervention duration and cancer diagnosis were assessed.
RESULTS
Twenty-two trials involving interventions ranging between 2 weeks and 6 months were included. Interventions comprised of aerobic (n = 3), resistance (n = 4), mixed-mode (n = 14) and other exercise (n = 1) modalities. Cancer types consisted of lung (n = 6), breast (n = 3), prostate (n = 2), multiple myeloma (n = 1) and mixed cancer types (n = 10). Meta-analysis of 20 RCTs involving 1840 participants showed no difference in the risk of a grade 2-4 adverse event between exercise and usual care (n = 110 adverse events (exercise: n = 66 events; usual care: n = 44 events), RD = - 0.01 (91% CI = - 0.01, 0.02); p = 0.24). Overall median recruitment, retention and adherence rates were 56%, 80% and 69%, respectively. Meta-analysis of health outcomes showed effects in favour of exercise for quality of life, fatigue, aerobic fitness and lower-body strength (SMD range = 0.27-0.48, all p < 0.05).
CONCLUSIONS
Participants who engaged in exercise experienced an increase in quality of life, fitness and strength and a decrease in fatigue.
IMPLICATIONS FOR CANCER SURVIVORS
Physical activity programs were found to be safe and feasible for people with advanced cancer in the palliative care phase.
Topics: Male; Humans; Quality of Life; Palliative Care; Cancer Survivors; Neoplasms; Exercise; Fatigue
PubMed: 35040076
DOI: 10.1007/s11764-021-01153-0 -
Diagnostics (Basel, Switzerland) Jun 2023The aim of this systematic review is to provide a comprehensive overview of the existing literature, comparing F-fluorodeoxyglucose (FDG) and C-methionine (MET) for the... (Review)
Review
The aim of this systematic review is to provide a comprehensive overview of the existing literature, comparing F-fluorodeoxyglucose (FDG) and C-methionine (MET) for the imaging of multiple myeloma (MM) with positron emission computed tomography (PET/CT). Relevant studies published from 2013 up to March 2023 were selected by searching Scopus, PubMed, and Web of Science. Selected imaging studies were analyzed using a modified version of the critical Appraisal Skills Programme (CASP). Ten studies encompassing 335 patients were selected. On a patient-based analysis, MET sensitivity ranged between 75.6% and 100%, resulting higher than that measured for FDG (0-100%). MET outperformed FDG for the detection of focal lesions, diffuse bone marrow involvement and mixed patterns. PET-derived parameters resulted higher for MET than for FDG, with a strong correlation with clinical variables (e.g., monoclonal component and beta-2-microglobulin levels, bone marrow infiltration, etc.), although FDG maintained a prognostic impact on outcome prediction. When compared to other tracers or imaging modalities, MET showed stronger correlation and inter-observer agreement than FDG. Although biased by the small cohorts and requiring confirmation through multicenter studies, preliminary findings suggest that MET-PET should be preferred to FDG for PET imaging of MM, or alternatively used as a complementary imaging modality. Some issues, such as tracer availability and the role of MET with respect to other emerging tracers (i.e., Ga-pentixafor, F-FACBC and F-FET), should be the topic of further investigations.
PubMed: 37370904
DOI: 10.3390/diagnostics13122009 -
Cancers May 2023Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development... (Review)
Review
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer's disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis.
PubMed: 37296934
DOI: 10.3390/cancers15112972 -
Synergistically Anti-Multiple Myeloma Effects: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib.Biomolecules Nov 2022Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has... (Review)
Review
Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has increased overall survival, progression-free survival, and remission rates in patients with MM since its clinical approval in 2003. However, the use of BTZ is challenged by the malignant features of MM and drug resistance. Polyphenols, classified into flavonoid and non-flavonoid polyphenols, have potential health-promoting activities, including anti-cancer. Previous preclinical studies have demonstrated the anti-MM potential of some dietary polyphenols. Therefore, these dietary polyphenols have the potential to be alternative therapies in anti-MM treatment regimens. This systematic review examines the synergistic effects of flavonoids and non-flavonoid polyphenols on the anti-MM impacts of BTZ. Preclinical studies on flavonoids and non-flavonoid polyphenols-BTZ synergism in MM were collected from PubMed, Web of Science, and Embase published between 2008 and 2020. 19 valid preclinical studies (Published from 2008 to 2020) were included in this systematic review. These studies demonstrated that eight flavonoids (icariin, icariside II, (-)-epigallocatechin-3-gallate, scutellarein, wogonin, morin, formononetin, daidzin), one plant extract rich in flavonoids (Punica granatum juice) and four non-flavonoid polyphenols (silibinin, resveratrol, curcumin, caffeic acid) synergistically enhanced the anti-MM effect of BTZ. These synergistic effects are mediated through the regulation of cellular signaling pathways associated with proliferation, apoptosis, and drug resistance. Given the above, flavonoids and non-flavonoid polyphenols can benefit MM patients by overcoming the challenges faced in BTZ treatment. Despite the positive nature of this preclinical evidence, some additional investigations are still needed before proceeding with clinical studies. For this purpose, we conclude by providing some suggestions for future research directions.
Topics: Humans; Bortezomib; Multiple Myeloma; Polyphenols; Apoptosis; Molecular Targeted Therapy; Cell Line, Tumor; Antineoplastic Agents; Drug Resistance, Neoplasm
PubMed: 36358997
DOI: 10.3390/biom12111647 -
Leukemia & Lymphoma Jun 2021Clinical trials may be inconsistent in their enrollment and reporting of patients with multiple myeloma (MM) who have renal insufficiency (RI). We performed a systematic... (Meta-Analysis)
Meta-Analysis
Clinical trials may be inconsistent in their enrollment and reporting of patients with multiple myeloma (MM) who have renal insufficiency (RI). We performed a systematic review of all MM randomized clinical trials (RCT) from 2005-2019 to evaluate reporting of prevalence, eligibility criteria and outcomes of patients with RI and MM. One-hundred and twenty-three RCTs were included. Only 30% of studies clearly reported on the proportion of patients who had RI. Only 68.2% reported eligibility criteria pertaining to RI, with no uniformity in the reported criteria. The relative risk (RR) of disease progression or death in patients with RI was higher than those without, RR of 1.20 (1.003-1.431) for relapsed/refractory and 1.07 (1.001-1.046) for newly diagnosed. There is inconsistent reporting and enrollment of patients with RI on MM RCT's. We advocate for higher enrollment of patients with RI and transparent reporting of their eligibility criteria and outcomes.
Topics: Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Renal Insufficiency
PubMed: 33416412
DOI: 10.1080/10428194.2020.1867725 -
Antibodies (Basel, Switzerland) May 2023Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific... (Review)
Review
Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19-63%, and VGPR in 21-65%. The common adverse events were cytokine release syndrome (17-82%), anemia (5-52%), neutropenia (12-75%), and thrombocytopenia (14-42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response.
PubMed: 37366654
DOI: 10.3390/antib12020038