The human monoclonal antibody daratumumab delivered intravenously has demonstrated single-agent efficacy as a monotherapy as well as significant efficacy in combination with standard-of-care regimens in patients with multiple myeloma who have received 1 or more prior lines of therapy.
Usmani and co-investigators tested subcutaneous delivery of daratumumab in combination with the recombinant human hyaluronidase enzyme (PH20) to facilitate systemic absorption of daratumumab into the abdominal wall. A total of 53 patients were treated subcutaneously with daratumumab-PH20, including 8 patients who received 1200 mg of daratumumab and 45 who received 1800 mg.
Subcutaneous infusion-related reactions (IRRs) were reported in 12 of 53 patients (23%); most were grade 1/2 in severity, including chills, fever, vomiting, edema of the tongue, noncardiac chest pain, and wheezing. No grade 4 IRRs were observed. All IRRs developed within 4 hours of the first subcutaneous injection; no reactions were reported with subsequent injections.
Overall, the adverse event profile of subcutaneous administration was consistent with intravenous daratumumab. Grade 3 or higher drug-related adverse events occurred in 23 of 53 patients (43%), including anemia, thrombocytopenia, neutropenia, lymphopenia, hypertension, and fatigue. Subcutaneous administration was well-tolerated at the abdominal wall injection site.
In the 1200-mg cohort, one-fourth of patients achieved an overall response, including 2 partial responses. Median time to response was 14 weeks. In the 1800-mg cohort, 38% of the evaluable responders achieved an overall response, including 1 complete response, 3 very good partial responses, and 13 partial responses. Median time to response was 4 weeks.
The authors concluded that the combination of subcutaneous daratumumab and PH20 was well-tolerated and achieved serum trough concentrations similar to or greater than intravenous daratumumab, with a lower rate of IRRs compared with intravenous delivery of the drug over a significantly shorter delivery time.
Usmani S, et al. ASH 2016. Abstract 1149.