No abstract

Lenalidomide (LEN), one of the immunomodulatory drugs (IMiDs), is widely used in combination with dexamethasone (DEX) to treat patients with multiple myeloma (MM), from primary to relapsed/refractory cases. Furthermore, LEN may also be administered in combination with a proteasome inhibitor (PI; bortezomib, carfilzomib or ixazomib) or an antibody drug (elotuzumab or daratumumab) and is a key drug for MM treatment. On the other hand, LEN is also known to have a higher incidence of skin rash compared with other IMiDs. [1][2][3] This may disrupt the treatment continuation and may also significantly reduce the patient's quality of life. The incidence of skin rash caused by Len is reported to be 9.7-50.0%. [4][5][6][7] There are a few case reports of desensitization therapies by LEN in patients with LEN-induced hypersensitivity and skin rash. [8][9][10][11][12] However, they are difficult to apply clinically since the schedule of administration is complicated or there is a risk that pharmacists may be exposed when preparing the drug. Therefore, we have changed the desensitization protocols reported previously to a simple one, which can be easily performed on elderly MM patients.

Gilteritinib, an oral inhibitor of FMS‐like tyrosine kinase 3 (FLT3), is a standard treatment for FLT3‐mutated acute myeloid leukemia. We developed a simple HPLC‐UV‐based method for determining the concentration of gilteritinib in human plasma. The analysis requires the extraction of a 200‐μL plasma sample and the precipitation of proteins by solid‐phase extraction. Gilteritinib was isocratically separated within 10 min using a mobile phase of acetonitrile:0.5% monopotassium phosphate (KH2PO4, pH 3.5, 28:72, v/v) on a Capcell Pack C18 MG II (250 × 4.6 mm) column at a flow rate of 1.0 mL/min and monitored at 250 nm. The calibration curve was found to be linear within a plasma concentration range of 25–2500 ng/mL, with the coefficient of determination (r2) being 0.9997. The coefficients of intra‐day and inter‐day validation were 2.3–3.7 and 1.3–5.2%, respectively. The accuracy and recovery of the assay were −9.6 to 0.1 and >81.8%, respectively. This HPLC‐UV method for determining the plasma concentration of gilteritinib is simple and can be effectively applied to routine drug monitoring.

What is known and objective It was previously reported that the incidence of lenalidomide (LEN)‐induced skin rash is reduced by administration of bortezomib (BOR) prior to LEN administration in patients with multiple myeloma (MM). Therefore, we investigated whether LEN‐induced skin rash is affected by the duration of BOR administration and the dosing interval between BOR and LEN administration. Method A retrospective investigation was conducted among MM patients who received BOR treatment prior to LEN treatment in Eiju General Hospital from May 2010 to December 2020. We investigated whether the BOR administration duration and interval duration from the completion of BOR administration to the initial LEN administration affect the development of LEN‐induced skin rash. Result and discussion Twenty‐eight of the 81 patients exhibited LEN‐induced skin rash (34.6%). The administered duration, but not the interval, was significantly longer in the group without skin rash. Cut‐off values were set for the duration of administration and interval, which were 35 days and 30 days, respectively. Multivariate analysis was performed on patients which are administered duration of more than 35 days and intervals of less than 30 days, and those who are not applicable. A significant difference was observed in the incidence of skin rash for each factor. What is new and conclusion The risk of reduced LEN‐induced skin rash is affected not only by the presence of prior BOR administration, but also by the duration of BOR and the interval from the completion of BOR to the initial LEN administration.