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JAMA Oncology Dec 2020Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML),... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.
OBJECTIVE
To examine the association between MRD status and disease-free survival (DFS) and overall survival (OS) in patients with AML using scientific literature.
DATA SOURCES
Clinical studies on AML published between January 1, 2000, and October 1, 2018, were identified via searches of PubMed, Embase, and MEDLINE.
STUDY SELECTION
Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies that assessed DFS or OS by MRD status in patients with AML were included. Reviews, non-English-language articles, and studies reporting only outcomes after hematopoietic cell transplantation or those with insufficient description of MRD information were excluded.
DATA EXTRACTION AND SYNTHESIS
Study sample size, median patient age, median follow-up time, MRD detection method, MRD assessment time points, AML subtype, specimen source, and survival outcomes were extracted. Meta-analyses were performed separately for DFS and OS using bayesian hierarchical modeling.
MAIN OUTCOMES AND MEASURES
Meta-analyses of survival probabilities and hazard ratios (HRs) were conducted for OS and DFS according to MRD status.
RESULTS
Eighty-one publications reporting on 11 151 patients were included. The average HR for achieving MRD negativity was 0.36 (95% bayesian credible interval [CrI], 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The estimated 5-year DFS was 64% for patients without MRD and 25% for those with MRD, and the estimated OS was 68% for patients without MRD and 34% for those with MRD. The association of MRD negativity with DFS and OS was significant for all subgroups, with the exception of MRD assessed by cytogenetics or fluorescent in situ hybridization.
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML. The value of MRD negativity appears to be consistent across age groups, AML subtypes, time of MRD assessment, specimen source, and MRD detection methods. These results support MRD status as an end point that may allow for accelerated evaluation of novel therapies in AML.
Topics: Bayes Theorem; Hematopoietic Stem Cell Transplantation; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Neoplasm, Residual; Prognosis
PubMed: 33030517
DOI: 10.1001/jamaoncol.2020.4600 -
BMC Medicine Dec 2022Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC).
METHODS
We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated.
RESULTS
In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 ± 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy.
CONCLUSIONS
In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Liquid Biopsy; Lung Neoplasms; Neoplasm Recurrence, Local
PubMed: 36514063
DOI: 10.1186/s12916-022-02681-x -
International Journal of Molecular... Jun 2023Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown... (Meta-Analysis)
Meta-Analysis Review
Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.
Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.
Topics: Humans; Circulating Tumor DNA; Neoplasm, Residual; Chemotherapy, Adjuvant; Colorectal Neoplasms; Biomarkers, Tumor; Neoplasm Recurrence, Local
PubMed: 37373376
DOI: 10.3390/ijms241210230 -
International Journal of Medical... 2021Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell... (Meta-Analysis)
Meta-Analysis
Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments. We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0). A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively. Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.
Topics: B-Cell Maturation Antigen; Clinical Trials as Topic; Drug Resistance, Neoplasm; Follow-Up Studies; Humans; Immunotherapy, Adoptive; Multiple Myeloma; Neoplasm Recurrence, Local; Progression-Free Survival; Receptors, Chimeric Antigen
PubMed: 33746596
DOI: 10.7150/ijms.46811 -
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 -
BMC Medicine May 2023The sensitivity and specificity of minimal residual disease detected by circulating tumor DNA profiling (ctDNA MRD) in lung cancer, with particular attention to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The sensitivity and specificity of minimal residual disease detected by circulating tumor DNA profiling (ctDNA MRD) in lung cancer, with particular attention to the distinction between landmark strategy and surveillance strategy, for predicting relapse in lung cancer patients after definitive therapy has yet to be determined.
METHODS
The prognostic value of ctDNA MRD by landmark strategy and surveillance strategy was evaluated in a large cohort of patients with lung cancer who received definitive therapy using a systemic literature review and meta-analysis. Recurrence status stratified by ctDNA MRD result (positive or negative) was extracted as the clinical endpoint. We calculated the area under the summary receiver operating characteristic curves, and pooled sensitivities and specificities. Subgroup analyses were conducted based on histological type and stage of lung cancer, types of definitive therapy, and ctDNA MRD detection methods (detection technology and strategy such as tumor-informed or tumor-agnostic).
RESULTS
This systematic review and meta-analysis of 16 unique studies includes 1251 patients with lung cancer treated with definitive therapy. The specificity of ctDNA MRD in predicting recurrence is high (0.86-0.95) with moderate sensitivity (0.41-0.76), whether shortly after treatment or during the surveillance. The landmark strategy appears to be more specific but less sensitive than the surveillance strategy.
CONCLUSIONS
Our study suggests that ctDNA MRD is a relatively promising biomarker for relapse prediction among lung cancer patients after definitive therapy, with a high specificity but suboptimal sensitivity, whether in landmark strategy or surveillance strategy. Although surveillance ctDNA MRD analysis decreases specificity compared with the landmark strategy, the decrease is minimal compared to the increase in sensitivity for relapse prediction of lung cancer.
Topics: Humans; Circulating Tumor DNA; Neoplasm, Residual; Lung Neoplasms; ROC Curve; Biomarkers, Tumor; Neoplasm Recurrence, Local
PubMed: 37173789
DOI: 10.1186/s12916-023-02849-z -
The Cochrane Database of Systematic... Sep 2021Cholangiocarcinoma (cancer in the bile duct) is an aggressive tumour for which surgical resection is a mainstay of treatment. Despite complete resection, recurrences of... (Review)
Review
BACKGROUND
Cholangiocarcinoma (cancer in the bile duct) is an aggressive tumour for which surgical resection is a mainstay of treatment. Despite complete resection, recurrences of the cancer are common and lead to poor prognosis in patients. Postoperative adjuvant chemotherapy given after surgical resection may reduce the risk of cancer recurrence by eradicating residual cancer and micrometastatic lesions. The benefits and harms of postoperative adjuvant chemotherapy versus placebo, no intervention, or other adjuvant chemotherapies are unclear.
OBJECTIVES
To assess the benefits and harms of postoperative adjuvant chemotherapy versus placebo, no intervention, or other adjuvant chemotherapies for people with cholangiocarcinoma after curative-intent resection.
SEARCH METHODS
We performed electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science for trials that met the inclusion criteria up to 28 April 2021.
SELECTION CRITERIA
Randomised clinical trials irrespective of blinding, publication status, or language comparing postoperative adjuvant chemotherapy versus placebo, no intervention, or a different postoperative adjuvant chemotherapy regimen for participants with curative-intent resection for cholangiocarcinoma.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods to develop and conduct the review. We conducted meta-analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CI). We assessed risk of bias according to predefined domains suggested by Cochrane. We rated the certainty of evidence using the GRADE approach and presented outcome results in a summary of findings table.
MAIN RESULTS
We included five published randomised clinical trials. The trials included 931 adults (18 to 83 years old) who underwent curative-intent resection for cholangiocarcinoma. Four trials compared postoperative adjuvant chemotherapy (mitomycin-C and 5-fluorouracil (5-FU); gemcitabine; gemcitabine plus oxaliplatin; or capecitabine) versus no postoperative adjuvant chemotherapy (surgery alone) in 867 participants with cholangiocarcinoma only. A fifth trial compared postoperative adjuvant S-1 (a novel oral fluoropyrimidine derivative) chemotherapy versus gemcitabine in 70 participants with intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma (64 participants), and gallbladder carcinoma (6 participants). We assessed all of the included trials at overall high risk of bias. One trial was conducted in France, three in Japan, and one in the United Kingdom. We could not perform all planned comparison analyses due to lack of data. Three trials used intention-to-treat analyses. Another trial used per-protocol analysis. In the remaining trial one participant in the intervention group and one in the control group were lost to follow-up. However, the outcomes of these two participants were not described. Postoperative adjuvant chemotherapy versus no postoperative adjuvant chemotherapy We are very uncertain as to whether postoperative adjuvant chemotherapy has little to no effect on all-cause mortality versus no postoperative adjuvant chemotherapy (RR 0.92, 95% CI 0.84 to 1.01; 4 trials, 867 participants, very low-certainty evidence). We are very uncertain of the effect of postoperative adjuvant chemotherapy on serious adverse events (RR 17.82, 95% CI 2.43 to 130.82; 1 trial, 219 participants, very low-certainty evidence). The trial indicated that postoperative adjuvant chemotherapy could increase serious adverse events, as 19/113 (20.5%) of participants developed an adverse event, compared to 1/106 (1.1%) of participants in the no-postoperative adjuvant chemotherapy group. None of the included trials reported data on health-related quality of life, cancer-related mortality, time to recurrence of the tumour, and non-serious adverse events in participants with only cholangiocarcinoma. Adjuvant S-1 chemotherapy (fluoropyrimidine derivative) versus adjuvant gemcitabine-based chemotherapy The only available trial analysed all participants with intrahepatic, perihilar cholangiocarcinoma and gallbladder carcinoma together, with data on participants with cholangiocarcinoma not provided separately. The authors reported that one-year overall mortality after adjuvant S-1 therapy was lower than with adjuvant gemcitabine-based therapy following major hepatectomy for biliary tract cancer. There were no differences in two-year overall mortality.
FUNDING
two trials received support from drug companies; one trial received funding from the Japan Society of Clinical Oncology; one trial received support from "Programme Hospitalier de Recherche Clinique (PHRC2009) and Ligue Nationale Contre le Cancer"; and one trial did not provide information on support or sponsorship. We identified six ongoing randomised clinical trials.
AUTHORS' CONCLUSIONS
Based on the very low-certainty evidence found in four trials in people with curative-intent resection for cholangiocarcinoma, we are very uncertain of the effects of postoperative adjuvant chemotherapy (mitomycin-C and 5-FU; gemcitabine; gemcitabine plus oxaliplatin; or capecitabine) versus no postoperative adjuvant chemotherapy on mortality. The effects of postoperative adjuvant chemotherapy compared with no postoperative adjuvant chemotherapy on serious adverse events are also very uncertain, but the result of the single trial showed 20% higher occurrences of haematologic adverse events. We assessed the certainty of the evidence as very low due to overall high risk of bias, and imprecision. Due to insufficient power of the only identified trial, the best postoperative adjuvant chemotherapy regimen in people with only cholangiocarcinoma could not be established. We also lack randomised clinical trials with outcome data on adjuvant S-1 chemotherapy versus adjuvant gemcitabine-based chemotherapy in people with cholangiocarcinoma alone. There is a need for further randomised clinical trials designed to be at low risk of bias and with adequate sample size exploring the best adjuvant chemotherapy treatment after surgery in people with cholangiocarcinoma.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemotherapy, Adjuvant; Cholangiocarcinoma; Humans; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Young Adult
PubMed: 34515993
DOI: 10.1002/14651858.CD012814.pub2 -
Annals of Medicine and Surgery (2012) Dec 2021Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the liver that can mimic hepatic angiosarcoma (AS) because of its infiltrative nature... (Review)
Review
BACKGROUND
Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the liver that can mimic hepatic angiosarcoma (AS) because of its infiltrative nature but is considered biologically less aggressive. We carried out a systematic review of the literature after previously coming across a case of HSVN [1] to guide our surveillance.
METHODS
We conducted a systematic review for all cases using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, case report journals and Google Scholar according to the PRISMA guidelines using the terms "hepatic small vessel neoplasm" or "hepatic small vessel neoplasia" with no language restrictions. The review was registered with Research Registry (UIN: reviewregistry1127) [2].
RESULTS
We identified 69 articles, of which 6 articles were eligible after screening. A total of 23 cases were identified. Median age was 58 (range 24-83 years) with a male preponderance (17 M:6F). Mean tumour size was 2.8 cm (range 0.2-15.9 cm). Mean follow-up was 7 months (range 1-24 months) with no reported evidence of recurrence in both patient groups with no residual disease or with positive margins after resection.
DISCUSSION
HSVN appears to demonstrate a benign clinical course with no reported recurrences or metastatic disease. Long-term follow-up data will further supplement our understanding of these tumours and guide future management.
PubMed: 34815856
DOI: 10.1016/j.amsu.2021.103004 -
International Journal of Molecular... Jun 2023Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral... (Meta-Analysis)
Meta-Analysis Review
A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis.
Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60-75% but fall to 5-15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.
Topics: Adult; Aged; Child; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Meta-Analysis as Topic; Neoplasm Recurrence, Local
PubMed: 37298623
DOI: 10.3390/ijms24119667 -
PloS One 2022Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely...
Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) were performed to identify randomized clinical trials (RCTs) and real-world studies in NDMM reporting median PFS and objective response. Associations between PFS and each response endpoint were evaluated using Pearson's product-moment correlation weighted by sample size in each RCT arm. Unadjusted and adjusted weighted linear regression models were applied to estimate the gain in median PFS associated with each response endpoint. Statistically significant correlations were identified for median PFS with overall response rate (ORR; Pearson r = 0.59), CR (r = 0.48), stringent CR (sCR; r = 0.68), and MRD (r = 0.69). The unadjusted models estimated 0.50 (95% CI: 0.36, 0.64; p<0.001), 0.42 (95% CI: 0.25, 0.58; p<0.001), 1.05 (95% CI: 0.58, 1.52; p<0.001), and 0.35 (95% CI: 0.12, 0.58; p = 0.006) months of median PFS gained per point of ORR, CR, sCR, and MRD, respectively. Associations for median PFS remained statistically significant in models adjusted for age and treatment type with ORR (0.35, 95% CI: 0.21, 0.49; p<0.001), and adjusted for age and International Staging System risk stage with CR (0.29, 95% CI: 0.16, 0.41; p<0.001). Due to small sample size, adjusted models could not be constructed for sCR or MRD. Nevertheless, evidence of significant survival benefit (p<0.05) associated with MRD negativity and sCR was identified across real-world studies. These findings provide support for the use of response outcomes as surrogate endpoints to estimate PFS benefit in NDMM.
Topics: Biomarkers; Disease-Free Survival; Humans; Multiple Myeloma; Neoplasm, Residual; Progression-Free Survival; Treatment Outcome
PubMed: 35550641
DOI: 10.1371/journal.pone.0267979