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.

High-throughput screening for amyloid-β binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC−DAD-Q/TOF-MS/MS

“…Therefore, most of the identified compounds are still in the stage of preclinical trial and discovery 55 , 56 . Of noted, FDA has just accepted the listing application of aducanumab, a monoclonal antibody targeting A β , based on the phase III clinical data on Alzheimer's early-stagy patients 57 . This application was recognized to be a landmark for new drugs.…”

Trends and Perspectives of Biological Drug Approvals by the FDA: A Review from 2015 to 2021

“…Like other conventional medicines, biologicals can undergo changes. One example is Darzalex TM (given intravenously), which was modified and approved in 2020 as Daratumumab and hyaluronidase (Darzalex Faspro TM ) (given subcutaneously), the latter containing the same combined human mAb with a recombinant human enzyme called hyaluronidase, which enhances the absorption of injectables, allows faster infusions, and a lower rate of reactions related to infusions [ 29 ]. Both Darzalex TM and Darzalex Faspro TM target CD38.…”

“…Another breakthrough in the period 2015–2021 was Poteligeo TM , a first-in-class biopharmaceutical that targets the CC chemokine receptor 4 (CCR4) [ 40 ]. In this period, we found four biologicals approved for multiple myeloma, but one of them (Empliciti TM ) has a distinct mechanism of action in that it binds to the cell surface receptor signaling lymphocytic activation molecule F7 (SLAMF7), whereas Darzalex TM , Darzalex Faspro TM and Sarclisa TM target CD38 [ 27 , 28 , 29 ]. Table 2 lists all the mAbs for cancer approved from 2015 to 2021 and detailed information for each one.…”

Immunotherapy of Multiple Myeloma: Promise and Challenges

“… 28 In addition, recent FDA approval of a subcutaneous (sc) formulation of daratumumab combined with hyaluronidase provides the substantial benefit of enabling markedly shorter administration times – 3–5 minutes vs several hours of intravenous (iv) infusion of the mAb without compromising efficacy or patient safety. 29–31 …”

“…28 In addition, recent FDA approval of a subcutaneous (sc) formulation of daratumumab combined with hyaluronidase provides the substantial benefit of enabling markedly shorter administration times -3-5 minutes vs several hours of intravenous (iv) infusion of the mAb without compromising efficacy or patient safety. [29][30][31] Infusion reactions, which include dyspnea, rash, headache, cough, nausea, vomiting, and nasal congestion represent an adverse, although generally low grade, effect of daratumumab, being noted in up to 50% of patients receiving the drug, especially during the first two infusions. Pre-medication with a glucocorticoid and/or a leukotriene blocker (montelukast) may help mitigate this effect and may be particularly useful in patients with underlying respiratory disease.…”