Chemotherapy‐induced nausea and vomiting (CINV) remains a major adverse event in cancer chemotherapy. Although aprepitant is effective in preventing CINV, an increment in financial burden for uniform use of aprepitant is a concern. The aim of the present study was to define the cost‐effectiveness of aprepitant from the perspective of the Japanese National Health Insurance system. Based on the results of a randomized phase II trial comparing an aprepitant‐containing regimen versus a nonaprepitant regimen in Japanese patients who received cisplatin‐containing highly emetogenic chemotherapy, a decision analytic model was developed. The incremental cost‐effectiveness ratio (ICER) was calculated both in the outpatient care setting (OCS) and in the inpatient care setting (ICS). The use of the aprepitant‐containing regimen was associated with improved quality of life compared with the nonaprepitant regimen, with an increment in quality‐adjusted life years (QALY) of 0.0016. The incremental total medical costs associated with the use of the aprepitant regimen were lower in the OCS than in the ICS, 6192 JPY (56.92 USD) and 9820 JPY (90.27 USD), respectively. The ICER was calculated as 3 906 698 JPY (35 910 USD) per QALY gained in the OCS and 6 195 781 JPY (56 952 USD) per QALY gained in the ICS. Cost‐effectiveness of the aprepitant‐containing antiemetic therapy was limited to the OCS, considering the threshold of willingness‐to‐pay commonly accepted (5 million JPY [45 960 USD] in Japan and 50 000 USD in the USA). The efficacy of aprepitant offsets the costs for revisiting clinics or rehospitalization added with rescue medications in the OCS.

In total knee and hip arthroplasty, methylprednisolone is effective in preventing postoperative nausea; however, higher doses of methylprednisolone may be needed to prevent vomiting.

Internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) confers poor prognosis and is found in approximately 25% of cases of acute myeloid leukemia (AML). Although FLT3 inhibitors have shown clinical benefit in patients with AML harboring FLT3-ITD, the therapeutic effect is limited. Here, to explore alternative therapeutics, we established a cellular model of monoallelic FLT3ITD/WT cells using the CRISPR-Cas9 system in a human myeloid leukemia cell line, K562. cDNA microarray analysis revealed elevated CD52 expression in K562–FLT3ITD/WT cells compared to K562–FLT3WT/WT cells, an observation that was further confirmed by quantitative real-time-PCR and flow cytometric analyses. The elevated expression of CD52 in K562–FLT3ITD/WT cells was decreased in wild-type FLT3 (FLT3-WT) knock-in K562–FLT3ITD/WT cells. In K562–FLT3ITD/WT cells, a STAT5 inhibitor, pimozide, downregulated CD52 protein expression while an AKT inhibitor, afuresertib, did not affect CD52 expression. Notably, an anti-CD52 antibody, alemtuzumab, induced significant antibody-dependent cell-mediated cytotoxicity (ADCC) in K562-FLT3ITD/WT cells compared to K562–FLT3WT/WT cells. Furthermore, alemtuzumab significantly suppressed the xenograft tumor growth of K562–FLT3ITD/WT cells in severe combined immunodeficiency (SCID) mice. Taken together, our data suggested that genetically modified FLT3-ITD knock-in human myeloid leukemia K562 cells upregulated CD52 expression via activation of STAT5, and alemtuzumab showed an antitumor effect via induction of ADCC in K562–FLT3ITD/WT cells. Our findings may allow establishment of a new therapeutic option, alemtuzumab, to treat leukemia with the FLT3-ITD mutation.

ObjectivesThis study assessed the cost-effectiveness of combination treatment with gemcitabine and cisplatin compared to treatment with gemcitabine alone for advanced biliary tract cancer (BTC) in Japan.MethodsA monthly transmitted Markov model of three states was constructed based on the Japan BT-22 trial. Transition probabilities among the health states were derived from a trial conducted in Japan and converted to appropriate parameters for our model. The associated cost components, obtained from a receipt-based survey undertaken at the Aichi Medical University Hospital, were those related to inpatient care, outpatient care, and treatment for BTC. Costs for palliative care and treatment of adverse events were obtained from the National Health Insurance price list. We estimated cost-effectiveness per quality-adjusted life year (QALY) at a time horizon of 36 months. An annual discount of 3 % for both cost and outcome was considered.ResultsThe base case outcomes indicated that combination therapy was less cost-effective than monotherapy when the incremental cost-effectiveness ratio (ICER) was approximately 14 million yen per QALY gained. The deterministic sensitivity analysis of the ICER revealed that the ICER of the base case was robust. A probabilistic analysis conducted with 10,000-time Monte Carlo simulations demonstrated efficacy at the willingness to pay threshold of 6 million yen per QALY gained for approximately 33 % of the population.ConclusionIn Japan, combination therapy is less cost-effective than monotherapy for treating advanced BTC, regardless of the statistical significance of the two therapies. Useful information on the cost-effectiveness of chemotherapy is much needed for the treatment of advanced BTC in Japan.

The prognosis of multiple myeloma (MM) has drastically improved owing to the development of new drugs, such as proteasome inhibitors and immunomodulatory drugs. Nevertheless, MM is an extremely challenging disease, and many patients are still refractory to the existing therapies, thus requiring new treatment alternatives. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 that shows efficacy in MM not only as a single agent but also in combination therapy, especially for MM patients with translocation t(11;14). However, many patients are refractory to this drug. Here, we treated the MM cell lines KMS12PE and KMS27 with a combination treatment of venetoclax targeting BCL-2 and daratumumab targeting CD38 to evaluate the synergistic cytotoxicity of these drugs in vitro. MM cell lines were co-cultured with natural killer (NK) cells at an effector:target ratio of 0.3:1 in the presence of serial concentrations of daratumumab and venetoclax, and the resulting apoptotic MM cells were detected by flow cytometry using annexin V. These results indicated that the antibody-dependent cell-mediated NK cytotoxicity was enhanced in KMS12PE and KMS27 cells harboring t(11;14) with a high BCL-2 expression, suggesting that the combination treatment of venetoclax and daratumumab should be especially effective in patients with these characteristics.