-
Hematology (Amsterdam, Netherlands) Dec 2024To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of... (Meta-Analysis)
Meta-Analysis
To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Multiple Myeloma; Transplantation, Autologous
PubMed: 38651865
DOI: 10.1080/16078454.2024.2343164 -
Annals of Palliative Medicine Jul 2021There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of lenalidomide in the treatment of multiple myeloma patients after allo-hematopoietic stem-cell transplantation: a systematic review and meta-analysis.
BACKGROUND
There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after allogeneic cell transplantation. This meta-analysis aimed to explore the effectiveness and safety of lenalidomide in the maintenance treatment of MM patients after allogeneic cell transplantation based on published data.
METHODS
A systematic review and meta-analysis was conducted in English and Chinese databases, covering all available publications until 1 December 2020. Statistical analysis was performed using the software STATA 14.0, and odds ratios (ORs) combined with 95% confidence intervals (CIs) were calculated to explore the efficacy and safety of lenalidomide in the treatment of MM patients after allogeneic cell transplantation.
RESULTS
A total of 173 MM cases in 8 independent studies from 2007 to 2014 were included. Through a single-arm meta-analysis of the disease status of MM patients after lenalidomide treatment, 3.6% of patients were in minimal response (MR, P=0.006), 39.0% were in complete remission (CR, P=0.169), 20.2% in partial remission (PR, P<0.001), 12.8% in very good partial remission (VGPR, P=0.049), and 9.7% in SD (P=0.023); the PD was 5.6% (P=0.010). Through meta-analysis of adverse reactions after taking lenalidomide, 35.3% (P=0.628) of participants developed acute graft-versus-host disease (GVHD); 22.6% (P=0.049) developed chronic GVHD; 20.3% (P=0.001) developed infection; 22.5% (P=0.352) had thrombocytopenia; 32.5% (P<0.000) had neutropenia; pain occurred in 17.8% (P=0.350) of patients, and peripheral neuropathy occurred in 17.8% (P=0.995) of participants. The overall survival (OS) of ≥2 years and progression-free survival (PFS) of ≥2 years of MM patients after allo-hematopoietic-stem-cell transplantation (HSCT) taking lenalidomide were analyzed, and the results were 64.9% (P=0.049) and 58.4% (P=0.890), respectively.
DISCUSSION
Lenalidomide is effective in the treatment of MM patients after allo-HSCT, and reducing the incidence of infection and peripheral neuropathy, but it is not effective in reducing GVHD and blood system adverse reactions.
Topics: Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Multiple Myeloma; Transplantation, Homologous; Treatment Outcome
PubMed: 34353061
DOI: 10.21037/apm-21-1598 -
Clinical Lymphoma, Myeloma & Leukemia Oct 2020Waldenström macroglobulinemia (WM) is an IgM-producing lymphoproliferative disorder that remains incurable. Patients with high-risk disease have an overall survival... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Waldenström macroglobulinemia (WM) is an IgM-producing lymphoproliferative disorder that remains incurable. Patients with high-risk disease have an overall survival (OS) of less than 3 years. Both autologous (AHCT) and allogeneic (allo-HCT) hematopoietic cell transplantation (HCT) are prescribed for treatment of WM despite a lack of randomized controlled studies.
MATERIALS AND METHODS
We performed a comprehensive literature search using PubMed/Medline and EMBASE on September 10, 2019. Data on clinical outcomes related to benefits and harms was extracted independently by 3 authors. Fifteen studies (8 AHCT [n = 278 patients], 7 allo-HCT [n = 311 patients]) were included in this systematic review/meta-analysis.
RESULTS
Pooled OS, progression-free survival (PFS), and nonrelapse mortality (NRM) rates post AHCT were 76% (95% confidence interval [CI], 65%-86%), 55% (95% CI, 42%-68%), and 4% (95% CI, 1%-7%), respectively. Pooled OS, PFS, and NRM rates post allografting were 57% (95% CI, 50%-65%), 49% (95% CI, 42%-56%), and 29% (95% CI, 23%-34%), respectively. OS and PFS rates were reported at 3 to 5 years, and NRM was reported at 1 year in most studies. Pooled ORR (at day 100) post AHCT and allo-HCT were 85% (95% CI, 72%-94%) and 81% (95% CI, 69%-91%), respectively. Pooled complete response rates post AHCT and allo-HCT were 22% (95% CI, 17%-28%) and 26% (95% CI, 7%-50%), respectively. Relapse rates post AHCT and allo-HCT were 42% (95% CI, 30%-55%) and 23% (95% CI, 18%-28%), respectively.
CONCLUSIONS
Our results show that both AHCT and allo-HCT are effective in the treatment of WM. A 2-fold lower relapse rate but a 7-fold higher NRM was noted for allo-HCT compared with AHCT. The role of transplant in WM needs to be addressed in the era of novel agents.
Topics: Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Waldenstrom Macroglobulinemia
PubMed: 32616401
DOI: 10.1016/j.clml.2020.05.021 -
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 -
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 -
Annals of Hematology Sep 2021Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug...
Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug conjugates (ADCs) and bispecific T-cell engagers are innovative immunotherapeutic approaches currently in development for the treatment of MM. This systematic review summarizes the efficacy and safety of ADCs and bispecific T-cell engagers in relapsed refractory (RR) MM patients from 2010 to date. Comprehensive literature search was conducted on PubMed, EMBASE, Wiley Cochrane Library, Web of Science, and Clinicaltrials.gov . A total of 13 studies (n = 529) met inclusion eligibility. All studies were prospective in nature investigating ADCs or bispecific T-cell engagers in RR MM; 10 trials were phase 1 and 3 were phase 2. The median age of patients ranged from 24 to 82 years. Among trials with ADC regimens, the overall response (OR) ranged from 34 to 60% and complete response (CR) ranged from 3 to 6%. The most common non-hematologic adverse event (AE) of ADCs was keratopathy, while anemia and thrombocytopenia were the most common hematological AEs. With bispecific T-cell engagers , ORR ranged from 31 to 83%, CR ranged from 7 to 22%, and partial response (PR) ranged from 5 to 16%. The most common non-hematologic AE of bispecific T-cell engagers was cytokine release syndrome (CRS) while the most common hematological AE was neutropenia. Initial data appears to show good clinical activity and tolerable safety profiles, making ADCs and bispecific T-cell engagers promising agents for RRMM. Future studies with newer combinations and a longer follow-up are needed to determine the precise role of these novel therapies in the evolving paradigm of MM treatment.
Topics: Animals; Antibodies, Bispecific; Antineoplastic Agents, Immunological; Humans; Immunoconjugates; Multiple Myeloma; Neoplasm Recurrence, Local; T-Lymphocytes
PubMed: 34318356
DOI: 10.1007/s00277-021-04599-5 -
Journal of Cancer Research and... Apr 2023Treatment of multiple myeloma has undergone significant advances in the last two decades, leading to meaningful improvement in overall and progression free survival. The... (Review)
Review
Treatment of multiple myeloma has undergone significant advances in the last two decades, leading to meaningful improvement in overall and progression free survival. The incurable nature of disease necessitates serial sequencing of treatment options and continuous therapy once disease remission is achieved. Autologous stem cell transplantation (ASCT) has continued to offer a meaningful survival advantage with a consistent reduction in toxicity and costs. Despite the advent of newer drugs leading to deeper and sustained responses, ASCT continues to be the standard of care for all eligible patients and is ostensibly more cost effective than continued treatment with newer agents. However, ASCT continues to be underutilized in India, due to concerns about cost, safety, and sporadic expertize. We present a systematic review of available data on ASCT for multiple myeloma from India to evaluate safety and efficacy of the procedure, and provide evidence re-affirming its utility in resource constrained settings.
Topics: Humans; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Progression-Free Survival; India
PubMed: 37147978
DOI: 10.4103/jcrt.jcrt_503_22 -
The Cochrane Database of Systematic... Oct 2012Several clinical studies have compared single with tandem (also called double) autologous stem cell transplantation (ASCT) as first-line treatment in patients with... (Review)
Review
First-line tandem high-dose chemotherapy and autologous stem cell transplantation versus single high-dose chemotherapy and autologous stem cell transplantation in multiple myeloma, a systematic review of controlled studies.
BACKGROUND
Several clinical studies have compared single with tandem (also called double) autologous stem cell transplantation (ASCT) as first-line treatment in patients with symptomatic multiple myeloma (MM), one of the leading indications for ASCT worldwide.
OBJECTIVES
The present Cochrane Review compares tandem autologous stem cell transplantation (TASCT) with single autologous stem cell transplantation (SASCT) as first-line treatment in patients with symptomatic MM with respect to overall survival (OS), event-free survival (EFS), quality of life (QoL) and treatment- or transplantation-related mortality.
SEARCH METHODS
We systematically identified controlled trials published between January 1995 and May 2011 in two bibliographic databases (MEDLINE and CENTRAL) and in clinical trial registries.
SELECTION CRITERIA
One researcher screened references for controlled trials to determine eligibility for the systematic review (SR) according to pre-specified inclusion and exclusion criteria, reflecting characteristics of disease and the interventions. We required a minimal set of details to be reported for observational studies for the studies to be included.
DATA COLLECTION AND ANALYSIS
We critically evaluated eligible trials with respect to quality of design and actual performance. One researcher extracted individual trial results, which were checked by another researcher. We recapitulated the results of the individual trials in a standardised way for the SR in order to allow a systematic assessment of potential sources of bias.
MAIN RESULTS
Overall, we identified 14 controlled studies. One registered randomised controlled trial (RCT) is still recruiting patients at the time of this review and no clinical results have been published. Two registered RCTs have remained unpublished despite their termination. Publications on one RCT had been retracted. We excluded five observational studies since neither patients nor treatment regimens were sufficiently characterised to allow an assessment of potential confounding by indication. We conducted a SR of study designs, definition of endpoints, treatment regimens and baseline characteristics of patients in the five included RCTs (two full-text publications, three conference presentations) enrolling1506 patients in total. Because we identified substantial clinical and methodological heterogeneity, we refrained from conducting a formal meta-analysis.While we included only previously untreated, symptomatic patients with MM the treatment regimens differed notably with respect to acute toxicity, between trials and also between study arms. Compared to state of the art treatment standards, the treatment regimens applied in all trials have to be considered as below standard from a contemporary perspective in at least one component.Three trials were likely to have the potential of being highly biased while two RCTs had a moderate potential for bias. The observed treatment effects in the set of included trials may have been influenced by a steep decrease in compliance with the second ASCT and the concomitant selection of patients. In addition, OS data were confounded by the treatment subsequent to first-line therapy.OS was statistically significantly improved in one trial only. While EFS was prolonged in four of the five trials, the median prolongation ranged between three to 12 months, with an uncertain direction of bias in the individual trials. QoL was not reported in any study. Results concerning treatment- or transplantation-related mortality could not be adequately assessed due to substantial differences in definitions between trials and low reporting quality.
AUTHORS' CONCLUSIONS
We did not consider any study to be sufficiently informative for contemporary treatment decisions concerning the question single versus tandem ASCT in view of inherent biases. In addition, none of the trials integrated the so-called "novel agents" which are now considered standard treatment for MM. To improve the quality of future studies, sample size calculations should consider the potentially steep decrease in compliance with the second ASCT. Reporting of results of treatment- or transplantation-related mortality should clearly specify the type and number of events (the numerator) in a well-defined population (the denominator).
Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow Transplantation; Combined Modality Therapy; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Multiple Myeloma; Quality of Life; Randomized Controlled Trials as Topic; Transplantation, Autologous
PubMed: 23076906
DOI: 10.1002/14651858.CD004626.pub3 -
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 -
Leukemia Research Reports 2017Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma.... (Review)
Review
Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma. We performed a systematic review and meta-analysis of studies to examine the association between regular aspirin use and risk of multiple myeloma. Five observational studies including 332,660 adults were evaluated. The pooled estimate had a hazard ratio of 0.90 (95% confidence interval =0.58-1.39; P=0.638). Odds ratios from the two case-control studies were similar. The findings demonstrated that there was no significant association between aspirin use and the risk of multiple myeloma.
PubMed: 28331798
DOI: 10.1016/j.lrr.2017.02.002