Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma

Abstract

Daratumumab, a human immunoglobulin G1 kappa monoclonal antibody that targets CD38, is currently approved as monotherapy and in varying combinations with approved anti-myeloma regimens in both newly diagnosed multiple myeloma and relapsed refractory multiple myeloma. Originally developed for intravenous administration, the subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) was recently approved by the US Federal Drug Administration and European Commission in 2020. In clinical trials, compared with the intravenous formulation, subcutaneous daratumumab (Dara-SC) has significantly shorter administration time (median first dose 7 h versus 3-5 min, respectively), lower rates of infusion-related reactions (median first dose 50% versus less than 10%, respectively), and lower volume of infusion (median 500-1000 ml versus 15 ml, respectively). Otherwise, the pharmacokinetics, safety profile, and efficacy are comparable. This review summarizes the pivotal trials that led to the approval of Dara-SC, highlights important clinical considerations for the use of Dara-SC, and provides practical guidelines for the administration of Dara-SC in the clinic.

Keywords: CD38; daratumumab; monoclonal antibody; multiple myeloma; myeloma; newly diagnosed; relapsed refractory; subcutaneous.

Figure 1.

Response and safety data in clinical trials of subcutaneous and intravenous daratumumab. d, dexamethasone; Dara-IV, intravenous daratumumab; Dara-SC, subcutaneous daratumumab; IRR, infusion-related reaction; M, melphalan; n, sample size; N/A, not applicable; ORR, overall response rate; P, prednisone; R, lenalidomide; V, bortezomib.

Figure 2.

Dosing and administration schema for subcutaneous daratumumab. C1D1, cycle 1, day 1; C1D8+, cycle 1, day 8 and thereafter; Dara-SC, subcutaneous daratumumab; Dex, dexamethasone; IV, intravenous.