This is the first report regarding the safety and blood levels of daratumumab after switching from IV to SC in patients with MM. The levels of daratumumab in the blood significantly increased after switching from IV to SC in the study population. During the safety evaluation for six months, newly developed grade 3 adverse events were not observed, except in one case of neutropenia. These findings indicate that SC of daratumumab is tolerable after switching from IV, and given its shorter administration time and lower IR rate, it would prove to be useful for the treatment of MM.

In this study, the median ratio of the SC/IV dose was approximately 2; however, the median ratio of the blood levels of SC/IV was only 1.4. This relationship between the dosage and blood levels may be explained by the bioavailability of SC. The bioavailability of SC has been reported to be approximately 70% [10]. Thus, parts of the administered daratumumab could have been metabolized before entering the blood circulation. As a result, the blood concentration of daratumumab might not have increased significantly despite the doublet dose.

In addition, a high inter-individual variability in the blood levels of daratumumab was observed in the assessed patients. Serum albumin levels, body weight, type of MM, and sex are known covariates of daratumumab PK parameters [10, 11]. The blood levels of daratumumab may have varied because of the differences in these covariates; the variability was much greater than the changes in the blood levels of daratumumab after switching from IV to SC.

The incidence of injection site reactions was 60% in this study; however, these were mild grade 1–2 adverse events in all cases, did not require discontinuation or additional treatment, and were resolved by the time of the next administration. In contrast, IR did not occur after switching to SC of daratumumab despite the increase in the dose. The only new serious adverse event of grade 3 or higher during six months of study period was one case of neutropenia. Overall, SC of daratumumab was tolerable by all 10 patients assessed in this study. Another study analyzing the safety after switching to SC of daratumumab further reported that this switching was safe in patients with transplant-ineligible newly diagnosed MM [12].

This study has several limitations. First, this was a small single-center study focusing on the safety and blood levels of daratumumab after switching from IV to SC, and other patients may show a different trend. Second, although safety was evaluated for six months, blood levels of daratumumab were only evaluated until two SC doses. Long-term changes in the blood levels of daratumumab upon administration of SC were not analyzed in this study. Third, the frequency of adverse events after switching the route of administration may not have been adequately evaluated due to the small number of patients involved. Fourth, in this study, we were concerned about an increase in adverse events, including myelosuppression, in patients with low body weight, but the number of patients was limited and we were not able to fully examine low body weight and obese patients.

In conclusion, the administration of daratumumab as SC has many benefits for patients, as it reduces the administration time and IR rate. Although fixed doses led to increased blood levels of daratumumab, the changes were minor compared to the inter-individual variability. Further, the adverse effects of SC of daratumumab were generally controllable. This suggests that switching from IV to SC of daratumumab is safe and reasonable for patients with MM.