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Frontiers in Oncology 2024Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side... (Review)
Review
Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.
PubMed: 38450195
DOI: 10.3389/fonc.2024.1324859 -
Cancers Nov 2021Novel therapies for multiple myeloma (MM) promise to improve outcomes but are also associated with substantial increasing costs. Evidence regarding cost-effectiveness of... (Review)
Review
BACKGROUND
Novel therapies for multiple myeloma (MM) promise to improve outcomes but are also associated with substantial increasing costs. Evidence regarding cost-effectiveness of novel treatments is necessary, but a comprehensive up-to-date overview of the cost-effectiveness evidence of novel treatments is currently lacking.
METHODS
We searched Embase, Medline via Ovid, Web of Science and EconLIT ProQuest to identify all cost-effectiveness evaluations of novel pharmacological treatment of MM reporting cost per quality-adjusted life year (QALY) and cost per life year (LY) gained since 2005. Quality and completeness of reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards.
RESULTS
We identified 13 economic evaluations, comprising 32 comparisons. Our results show that novel agents generate additional LYs (range: 0.311-3.85) and QALYs (range: 0.1-2.85) compared to backbone regimens and 0.02 to 1.10 LYs and 0.01 to 0.91 QALYs for comparisons between regimens containing two novel agents. Lifetime healthcare costs ranged from USD 60,413 to 1,434,937 per patient. The cost-effectiveness ratios per QALY gained ranged from dominating to USD 1,369,062 for novel agents compared with backbone therapies and from dominating to USD 618,018 for comparisons between novel agents.
CONCLUSIONS
Cost-effectiveness ratios of novel agents were generally above current willingness-to-pay thresholds. To ensure access, cost-effectiveness should be improved or cost-effectiveness ratios above current thresholds should be accepted.
PubMed: 34830761
DOI: 10.3390/cancers13225606 -
Cancer Jun 2020Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each... (Meta-Analysis)
Meta-Analysis
Association of adverse events and associated cost with efficacy for approved relapsed and/or refractory multiple myeloma regimens: A Bayesian network meta-analysis of phase 3 randomized controlled trials.
BACKGROUND
Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs).
METHODS
Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs).
RESULTS
Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60).
CONCLUSIONS
The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Bortezomib; Clinical Trials, Phase III as Topic; Dexamethasone; Drug Costs; Humans; Lenalidomide; Multiple Myeloma; Oligopeptides; Progression-Free Survival; Randomized Controlled Trials as Topic; Thalidomide; Treatment Outcome
PubMed: 32154922
DOI: 10.1002/cncr.32831 -
Experimental and Therapeutic Medicine Aug 2019Multiple myeloma (MM) remains incurable primarily due to relapse. Histone deacetylase inhibitors (HDACis) have shown potential application for the treatment of...
Multiple myeloma (MM) remains incurable primarily due to relapse. Histone deacetylase inhibitors (HDACis) have shown potential application for the treatment of relapsed/refractory multiple myeloma (RRMM). To assess the efficacy and safety of HDACis in RRMM treatment, a systematic review and meta-analysis were conducted based on clinical trial data. A literature search was performed using PubMed, EMBASE, Web of Science and the Cochrane Library databases. Subsequently, 19 trials with 2193 patients treated with one of the three HDACis, panobinostat, ricolinostat and vorinostat, were identified and included in the present study. The efficacy and toxicity of each agent were assessed. The data were pooled using a random effects model in STATA 13.0. The results showed that the overall response rate (ORR) was 0.64 with a 95% confidence interval (CI) of 0.61-0.68 for panobinostat, 0.51 (95% CI, 0.46-0.55) for vorinostat and 0.38 (95% CI, 0.29-0.48) for ricolinostat. Additionally, subgroup analysis revealed an ORR of 0.36 (95% CI, 0.27-0.46) for HDACis-treated bortezomib-refractory MM patients and 0.43 (95% CI, 0.30-0.55) for lenalidomide-refractory patients. The most common grade 3 and 4 hematological adverse events were thrombocytopenia, neutropenia and anemia. Non-hematological adverse events included fatigue/asthenia, diarrhea and nausea. In conclusion, analysis of the pooled data revealed that panobinostat-containing regimens were effective and tolerable for patients with RRMM. Furthermore, lenalidomide-refractory patients may derive greater benefits from these regimens. More clinical and real-world studies are required to validate these results.
PubMed: 31363365
DOI: 10.3892/etm.2019.7704 -
Scientific Reports Jun 2016During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer... (Meta-Analysis)
Meta-Analysis Review
During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31-0.59, I(2)ā=ā90.5%, Pā=ā0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Hydroxamic Acids; Indoles; Multiple Myeloma; Panobinostat; Recurrence; Treatment Outcome
PubMed: 27270478
DOI: 10.1038/srep27361