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European Journal of Haematology Jun 2017We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM).
METHODS
Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality.
RESULTS
Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results.
CONCLUSIONS
This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Regression Analysis; Remission Induction; Survival Analysis; Transplantation, Autologous; Treatment Outcome
PubMed: 28178364
DOI: 10.1111/ejh.12868 -
Annals of Hematology Dec 2022With the incorporation of novel agents in earlier lines of therapy, an increasing number of multiple myeloma patients are refractory to traditional classes of drugs.... (Review)
Review
With the incorporation of novel agents in earlier lines of therapy, an increasing number of multiple myeloma patients are refractory to traditional classes of drugs. Selinexor in combination with dexamethasone has emerged as a viable option for heavily pretreated triple-class relapsed and refractory multiple myeloma (RRMM). In this systematic review, we analyzed available literature on the role of selinexor in RRMM. The Boston trial demonstrated that selinexor when combined with dexamethasone and bortezomib is associated with a better depth and duration of response without excessive toxicity, compared with bortezomib and dexamethasone alone. Similarly, selinexor in combination with carfilzomib and dexamethasone was found to have a durable response and tolerable safety profile in both carfilzomib-naive and carfilzomib refractory RRMM patients. Selinexor in combination with IMiDs (lenalidomide and pomalidomide) as well as CD38 monoclonal antibodies (daratumumab) also have promising results. Selinexor combination therapy is both safe and effective for patients with pretreated RRMM.
Topics: Humans; Multiple Myeloma; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Neoplasm Recurrence, Local
PubMed: 36214853
DOI: 10.1007/s00277-022-04999-1 -
JAMA Oncology Mar 2018Cardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE.
OBJECTIVE
To determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies.
DATA SOURCES
PubMed, EMBASE, Web of Science, and clinicaltrials.gov were queried for the keywords "carfilzomib," "Kyprolis," and "PX-171" through January 1, 2017.
STUDY SELECTION
Phase 1 to 3 prospective clinical trials of carfilzomib in patients with multiple myeloma with evaluable toxic effects data were eligible for meta-analysis.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Pooled incidence rates and relative risks (for randomized trials) and 95% confidence intervals were calculated using a random effects model. Subgroup analyses were performed to assess study-level characteristics associated with CVAE.
MAIN OUTCOMES AND MEASURES
Cardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grades 3 or higher AEs and study characteristics were recorded.
RESULTS
A total of 514 studies were assessed for eligibility. Of those, 24 studies were eligible, including a total of 2594 patients with multiple myeloma. All-grade and grades 3 and higher CVAE were seen in 617 (18.1%) and 274 (8.2%), respectively. Phase 2 or 3 studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade CVAE. Median age older than 65 years, prior myeloma therapies, and concurrent myeloma therapies were not associated with CVAE. For the 3 randomized clinical trials, the summary relative risk of all-grade and grade 3 or higher CVAE for patients receiving carfilzomib compared with noncarfilzomib-receiving control patients were 1.8 and 2.2, respectively.
CONCLUSIONS AND RELEVANCE
Carfilzomib was associated with a significant incidence of CVAE, with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting CVAE. Future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.
Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Humans; Incidence; Middle Aged; Multiple Myeloma; Oligopeptides; Proteasome Inhibitors; Randomized Controlled Trials as Topic
PubMed: 29285538
DOI: 10.1001/jamaoncol.2017.4519 -
Orphanet Journal of Rare Diseases Jul 2022Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of...
BACKGROUND
Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition.
METHODS
This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data.
RESULTS
Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively.
CONCLUSIONS
Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options.
Topics: Europe; Humans; Immunoglobulin Light-chain Amyloidosis; Incidence; Prevalence; Registries; United States
PubMed: 35854312
DOI: 10.1186/s13023-022-02414-6 -
Drug and Chemical Toxicology Jul 2022Prolonged survival and expanded treatment options in myeloma patients have led to adverse events associated with treatment getting increased attention. This systematic... (Meta-Analysis)
Meta-Analysis
Prolonged survival and expanded treatment options in myeloma patients have led to adverse events associated with treatment getting increased attention. This systematic review and meta-analysis aimed to determine the incidence of ixazomib-associated cardiovascular adverse events (CVAEs) and to compare the rates of ixazomib-associated CVAEs and related therapies. CVAEs were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and high-grade CVAEs and study characteristics were recorded. A total of 266 potentially relevant articles were identified, and 246 were excluded after review. Twenty studies of 1715 patients with multiple myeloma were thus considered in this study. The estimated rates of all-grade and high-grade ixazomib associated CVAEs were 11.2 and 3.7%, respectively. Subgroup analysis showed that median age ≥65 years, none phase 1 trial and combination regimen were associated with higher rates of high-grade ixazomib associated CVAEs. Ixazomib was association with increased high-grade CVAEs risk (RR = 1.679, 95% CI: 1.078-2.615, = 0.022). Ixazomib was associated with a significant rate of high-grade CVAEs. Future studies are needed to identify patients at high risk for high-grade CVAEs.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boron Compounds; Glycine; Humans; Hypertension; Multiple Myeloma
PubMed: 33108916
DOI: 10.1080/01480545.2020.1835945 -
PloS One 2013In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a meta-analysis of RCTs examining the efficacy and safety of lenalidomide for MM.
PATIENTS AND METHODS
Databases were searched using the terms "lenalidomide or revlimid AND multiple myeloma."RCTs evaluating initial or maintenance therapeutic outcomes were included. Main outcome measures were response rates, progression-free survival (PFS), overall survival, and adverse events.
RESULTS
Seven trials were included (N = 192-614 participants). Lenalidomide doses and treatment regimens differed between trials. Complete response (CR) and very good partial response (VGPR) risk ratios (RR) favored lenalidomide over placebo (CR = 2.54, 95% confidence interval [CI] = 1.29-5.02; VGPR = 2.82, 95% CI = 1.30-6.09). The PFS hazard ratio favored lenalidomide over placebo (0.37, 95% CI = 0.33-0.41). For adverse events, neutropenia, deep vein thrombosis (DVT), infection, and hematologic cancer RR favored placebo over lenalidomide (neutropenia: 4.74, 95% CI = 2.96-7.57; DVT: 2.52; 95% CI: 1.60-3.98; infection: 1.98; 95% CI: 1.50-2.62; hematologic cancer: 3.20; 95% CI: 1.28-7.98).
CONCLUSIONS
Lenalidomide is an effective treatment for MM; however, treatment-related adverse events must be considered and appropriate adjustments and/or prophylactic treatment should be initiated where possible.
Topics: Disease-Free Survival; Humans; Lenalidomide; Multiple Myeloma; Neoplasms, Second Primary; Randomized Controlled Trials as Topic; Thalidomide; Treatment Outcome
PubMed: 23691202
DOI: 10.1371/journal.pone.0064354 -
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 -
Oncotarget Jul 2017The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections... (Meta-Analysis)
Meta-Analysis Review
The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections have been associated with its use. In this meta-analysis, we assessed the overall risk of infection to MM patients treated with lenalidomide. Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial Registration website, and from meeting abstracts and virtual presentations at the American Society of Clinical Oncology. Main outcome measures were overall incidence, relative risk (RR), and 95% confidence intervals (CIs) of reported infection events. Fixed-effect or random-effect models were used in the statistical analyses, depending on the between-study heterogeneity. The overall incidence of high-grade infection was 14.32% (95% CI: 12.08%-16.90%) and high-grade infection's pooled RR was 2.23 (95% CI: 1.71-2.91, P < 0.0001) for all 11 studies evaluated. No evidence of publication bias for the incidence of high-grade infection was detected using Begg's funnel plot and Egger's test (P = 0.2; 95% CI: -1.70, 1.23). From this meta-analysis, it appears lenalidomide use is associated with an increased risk of high-grade infection. Moreover, fatal infection events occurred only in patients treated with lenalidomide; no infection-related deaths were observed among controls. These data indicate that accurate diagnosis and optimal management of infection in MM patients treated with lenalidomide could be critical for treatment efficacy.
Topics: Antineoplastic Agents; Humans; Immunologic Factors; Incidence; Infections; Lenalidomide; Mortality; Multiple Myeloma; Publication Bias; Risk; Severity of Illness Index; Thalidomide
PubMed: 28423741
DOI: 10.18632/oncotarget.16235 -
European Journal of Cancer (Oxford,... Nov 2016The objective of this review was to determine the impact of immunomodulatory drugs (IMiDs) and proteasome inhibitor (PI)-based therapy on infection risk in patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The objective of this review was to determine the impact of immunomodulatory drugs (IMiDs) and proteasome inhibitor (PI)-based therapy on infection risk in patients with myeloma across three treatment periods: induction, maintenance therapy and relapse/refractory disease (RRMM).
METHODS
A systematic review and meta-analysis of randomised controlled trials (RCT) of IMiD and PI-based therapy versus conventional therapy from 1990 to 2015 using MEDLINE, EMBASE and CENTRAL was conducted. Study methods, characteristics, interventions, outcomes and rate of infection were extracted using a standardised tool.
FINDINGS
Thirty RCTs of 13,105 patients fulfilled inclusion criteria. The rate of severe infection with the use of IMiD-based therapy was 13.4%, 22.4%, 10.5% and 16.6% for induction therapy for non-transplant- and transplant-eligible patients, maintenance therapy and therapy for RRMM, respectively. Rate of severe infection with PI-based induction in transplant-eligible patients was 19.7%. Compared to conventional therapy, use of IMiD-based induction therapy was associated with reduced risk for transplant patients (RR 0.76, p < 0.01). There was no significant difference with PI-based therapy. For maintenance therapy and RRMM, use of IMiD-based therapy was significantly associated with 74% and 51% increased risk of severe infection, respectively. Compared to thalidomide, bortezomib-based induction therapy and lenalidomide maintenance therapy were associated with increased risk of severe infection (RR 2.03, p < 0.01; RR 1.95, p = 0.03).
INTERPRETATION
The differential impact of myeloma therapies on risk for infection and the effect of treatment phases upon risk have now been established. Thalidomide is associated with the lowest risk of severe infection when used for induction and maintenance therapy.
FUNDING
Fight Cancer Foundation.
Topics: Antineoplastic Agents; Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Induction Chemotherapy; Infections; Lenalidomide; Maintenance Chemotherapy; Multiple Myeloma; Proteasome Inhibitors; Randomized Controlled Trials as Topic; Risk; Thalidomide
PubMed: 27592069
DOI: 10.1016/j.ejca.2016.07.025 -
Annals of Medicine Dec 2024The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with... (Meta-Analysis)
Meta-Analysis
AIM
The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile.
METHODS
We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760).
RESULTS
Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80).
CONCLUSIONS
This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.
Topics: Humans; Hematopoietic Stem Cell Mobilization; Multiple Myeloma; Granulocyte Colony-Stimulating Factor; Heterocyclic Compounds; Lymphoma; Lymphoma, Non-Hodgkin; Hematopoietic Stem Cells; Transplantation, Autologous; Benzylamines; Hematopoietic Stem Cell Transplantation
PubMed: 38470973
DOI: 10.1080/07853890.2024.2329140