Toward further simplification of elotuzumab therapy by subcutaneous administration
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LETTER TO THE EDITOR
Toward further simplification of elotuzumab therapy by subcutaneous administration Yuji Shimura1 · Taku Tsukamoto1 · Junko Yamaguchi1 · Saeko Kuwahara‑Ota1 · Reiko Isa1 · Daichi Nishiyama1 · Tsutomu Kobayashi1 · Shigeo Horiike1 · Atsushi Suzuki2 · Junya Kuroda1 Received: 27 May 2020 / Revised: 15 June 2020 / Accepted: 23 June 2020 © Japanese Society of Hematology 2020
Keywords Subcutaneous · Elotuzumab · Multiple myeloma Signaling lymphocyte activation molecule F7 (SLAMF7) is strongly expressed on the surface of multiple myeloma (MM) cells, and therefore, constitutes a disease-specific therapeutic target for MM. Elotuzumab (ELO), a humanized IgG1 monoclonal antibody (MoAb) against SLAMF7, is one of the central treatment agents for MM, especially in combination with lenalidomide or pomalidomide in the presence of dexamethasone. Several clinical trials, such as that by Kubo et al. reported in the recent issue of International Journal of Hematology [1], have nicely validated the efficacy and feasibility of the high-speed infusion of ELO at 5 mL/ min, which is 2.5-fold faster than the originally adopted infusion rate at 2 mL/min in ELOQUENT-2 study. As discussed by authors [1], this “faster” intravenous (IV) strategy allows most infusion to be completed within 1 h, reduces patients’ physical burden without increase of adverse events, and potentially saves medical resources. To further develop a safe and more convenient route, we herein sought to explore the possibility for subcutaneous (SC) administration of ELO using mice experimental model. For this study, we newly established an ELISA for measurement of ELO in serum. The establishment and the quality Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12185-020-02942-6) contains supplementary material, which is available to authorized users. * Yuji Shimura [email protected]‑m.ac.jp * Junya Kuroda [email protected]‑m.ac.jp 1
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii‑cho, Kamigyo‑ku, Kyoto 602‑8566, Japan
Oncology Division, Bristol-Myers Squibb K.K, Shinjuku, Tokyo 163‑1327, Japan
2
validation of this assay system were described in Supplementary information. Using this ELISA assay, we examined the utility of SC delivery of ELO in mice by pharmacokinetic analysis. ELO was provided by Bristol-Myers Squibb (Princeton Pike, NJ), and was dissolved at 1 mg/mL in distilled water (DW). Six-week-old male Crl:CD1 mice (Charles River Laboratories Japan) were used in the study. With adjustment for body weight on the day before experiments, 30 mice were divided into SC and intraperitoneal (IP) treatment groups. Each group consisted of 15 mice and the mean body weight was similar in the two groups: 33.4 g and 33.2 g in the SC and IP groups, respectively. ELO was injected at 10 mg/kg (same as the dose clinically used) as a single dose subcutaneously on the back (SC group) or directly into the peritoneal cavity (IP group). Serum conc
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