Cost-effectiveness of polatuzumab vedotin combined with chemoimmunotherapy in untreated diffuse large B-cell lymphoma.

In patients with treatment-naive diffuse large B-cell lymphoma (DLBCL), the POLARIX study (A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone [R-CHP] Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [R-CHOP] in Participants With Diffuse Large B-Cell Lymphoma) reported a 6.5% improvement in the 2-year progression-free survival (PFS), with no difference in overall survival (OS) or safety using polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) compared with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We evaluated the cost-effectiveness of pola-R-CHP for DLBCL. We modeled a hypothetical cohort of US adults (mean age, 65 years) with treatment-naive DLBCL by developing a Markov model (lifetime horizon) to model the cost-effectiveness of pola-R-CHP and R-CHOP using a range of plausible long-term outcomes. Progression rates and OS were estimated from POLARIX. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $150 000 per quality-adjusted life-year (QALY). Assuming a 5-year PFS of 69.6% with pola-R-CHP and 62.7% with R-CHOP, pola-R-CHP was cost-effective at a WTP of $150 000 (incremental cost-effectiveness ratio, $84 308/QALY). pola-R-CHP was no longer cost-effective if its 5-year PFS was 66.1% or lower. One-way sensitivity analysis revealed that pola-R-CHP is cost-effective up to a cost of $276 312 at a WTP of $150 000. pola-R-CHP was the cost-effective strategy in 56.6% of the 10 000 Monte Carlo iterations at a WTP of $150 000. If the absolute benefit in PFS is maintained over time, pola-R-CHP is cost-effective compared with R-CHOP at a WTP of $150 000/QALY. However, its cost-effectiveness is highly dependent on its long-term outcomes and costs of chimeric antigen receptor T-cell therapy. Routine usage of pola-R-CHP would add significantly to health care expenditures. Price reductions or identification of subgroups that have maximal benefit would improve cost-effectiveness.

Acute oral toxicity test and assessment of combined toxicity of cadmium and aflatoxin B1 in kunming mice.

Cadmium and aflatoxin B1 (AFB1) are both common and widespread pollutants in food and feed. There are several reports on toxicity induced by Cadmium or AFB1 alone, but few address the toxicity caused by co-exposure to the two substances. In this study, 42 female and 42 male Kunming (KM) mice were divided into seven groups to test the acute oral toxicity of CdCl2 and AFB1, using Karber's method. The combined toxicity was assessed using the Keplinger evaluation system. Acute toxicity symptoms, deaths, and body and organ weights were evaluated, and hematological, blood biochemical, and histopathological analyses were conducted. The results revealed the following median lethal doses (LD50): LD50(Female KM mice) = 62.56 mg/kg; LD50(Male KM mice) = 48.79 mg/kg; LD50(KM mice)=55.27 mg/kg. The combined toxicity of AFB1 and CdCl2 showed an additive effect in mice, and an increase in the mixed dose of AFB1 and CdCl2 resulted in greater toxicity. These results demonstrated that the combined toxicity of AFB1 and CdCl2 was greater than the toxicities of the individual components in mice; thus, this may cause particular challenges when addressing these hazards in food and feed and the associated risk to human and animal health.