Cost-Effectiveness Analysis of Adding Daratumumab to Bortezomib, Melphalan, and Prednisone for Untreated Multiple Myeloma.

Background: To evaluate the cost-effectiveness of adding daratumumab to bortezomib, melphalan, and prednisone for transplant-ineligible newly diagnosed multiple myeloma patients. Methods: A three-state Markov model was developed from the perspective of US payers to simulate the disease development of patient's life time for daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) and bortezomib, melphalan, and prednisone (VMP) regimens. The primary outputs were total costs, expected life-years (LYs), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results: The base case results showed that adding daratumumab to VMP provided an additional 3.00 Lys or 2.03 QALYs, at a cost of $262,526 per LY or $388,364 per QALY. Sensitivity analysis indicated that the results were most sensitive to utility of progression disease of D-VMP regimens, but no matter how these parameters changed, ICERs remained higher than $150,000 per QALY. Conclusion: In the case that the upper limit of willingness to pay threshold was $150,000 per QALY from the perspective of US payers, D-VMP was not a cost-effective regimen compared to VMP.

Treatment Outcomes in Patients With Newly Diagnosed Multiple Myeloma Who Are Ineligible for Stem-Cell Transplantation: Systematic Review and Network Meta-analysis.

Many new regimens have been applied to newly diagnosed transplant-ineligible multiple myeloma, but no head-to-head research has been performed to compare the efficacy of these treatments. Currently lenalidomide plus dexamethasone (Rd) is one of the standard treatments. Our aim was to make a comparison of these treatments to Rd by a network meta-analysis. We performed a systematic review and network meta-analysis. We searched PubMed, Embase, and the Cochrane Library for articles published from January 1, 1988, to April 26, 2018, as well as research presented at 5 international conferences (American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, European Society of Medical Oncology, and International Myeloma Working Group) between January 2015 and December 2018. Our interest outcomes were hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS). Bayesian fixed-effects mixed-treatment comparisons were used for this study. A total of 23 articles describing 10,401 participants were included for this network meta-analysis. Lenalidomide and dexamethasone plus daratumumab (HR, 0.57; 95% credible interval [CrI], 0.43-0.73), daratumumab plus bortezomib, melphalan, and prednisone (HR, 0.59; 95% CrI, 0.36-0.91), and the combination of bortezomib with lenalidomide and dexamethasone (RVd) (HR, 0.72, 95% CrI, 0.56-0.90) all showed significant effect compared to Rd for PFS. RVd demonstrated significant benefit compared to Rd (HR, 0.72; 95% CrI, 0.53-0.96) for OS. Our study results suggested that lenalidomide and dexamethasone plus daratumumab; daratumumab plus bortezomib, melphalan, and prednisone; and RVd showed better efficacy than Rd in PFS; and RVd showed better efficacy than Rd in OS in patients with newly diagnosed transplant-ineligible multiple myeloma in the absence of head-to-head research.

Efficacy and safety of Levetiracetam as adjunctive treatment in children with focal onset seizures: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive treatment in children (0-18 years) with focal-onset seizures (FOS) with a larger dataset. METHODS: A pooled analysis would be performed for prospective clinical trials and a meta-analysis for controlled studies. Retrospectives studies were also summarized using descriptive statistics. RESULTS: Thirty-one articles (1763 patients) were identified, eighteen prospective self-controlled studies and thirteen retrospective studies. LEV was more effective than placebo, the pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the 50% responder rate, seizure freedom rate and the median percentage reduction rate were 1.98 (1.49-2.63), 5.12 (2.09-12.51) and 3.19 (2.37-4.30), respectively. The overall response rates (ORRs) and 95% CIs were 56% (52%-60%), 14% (9%-19%) and 55% (31%-79%), respectively. For safety assessment, the pooled RRs and 95% CIs for the at least one treatment-emergent adverse events (TEAE) rate and at least one adverse drug reactions related (ADR-related) TEAE rate were 1.03 (0.94-1.13) and 1.45 (1.13-1.86) between two group. The ORRs and 95% CIs were 74% (54%-94%) and 48% (40%-55%). The adverse events significantly associated with LEV were somnolence 2.26 (95% CI 1.30-3.93) and hostility 2.33 (95% CI 1.15-4.70). The most frequency adverse events were pyrexia, headache, nervousness, upper respiratory tract and somnolence. The RRs for withdrawal rate or the ADR-related withdrawal rate were 0.77 (95% CI 0.44-1.38) and 0.91 (0.42-1.98), the ORRs were 17% (5%-28%) and 6% (4%-8%). CONCLUSION: The meta-analysis suggested that add-on LEV can significantly reduce seizure frequency and fairly tolerated compared to placebo.