Update on Role of Subcutaneous Daratumumab in Multiple Myeloma
Posted: Monday, July 27, 2020
According to Ajai Chari, MD, PhD, of Mount Sinai School of Medicine, New York, and colleagues, subcutaneous injection of daratumumab in combination with recombinant human hyaluronidase PH20 (rHuPH20) achieved trough concentrations similar to or greater than those with intravenous daratumumab in patients with relapsed or refractory multiple myeloma. The results from Part 2 of the PAVO phase Ib trial, which were published in Haematologica, demonstrated this formulation may reduce administration time and lower rates of infusion-related reactions.
“Daratumumab is an [approved] human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action,” the investigators stated. “Recombinant human hyaluronidase PH20 depolymerizes hyaluronan in the subcutaneous space, allowing rapid administration of large volumes of injected drugs, thus facilitating subcutaneous delivery.”
The subcutaneous injection of a mix-and-deliver formulation of daratumumab and rHuPH20 (1,200 mg and 1,800 mg) appeared to be safe and effective in patients with multiple myeloma, according to the results from Part 1 of the PAVO study. Thus, the investigators developed the subcutaneous combination of daratumumab and rHuPH20 at 1,800 mg with a lower injection volume (15 vs. 60 and 90 mL) and shorter injection time (3–5 vs. 20 to 30 minutes). Twenty-five patients with relapsed or refractory disease who received at least two prior lines of therapy were enrolled in Part 2. Follow-up data were provided for an average of 14.2 months.
In addition to having similar daratumumab trough concentrations at the end of weekly dosing, the subcutaneous and intravenous daratumumab regimens exhibited comparable safety profiles. Infusion-related reactions occurred in 16% of patients treated with the subcutaneous therapy. The investigators reported an overall response rate of 52%, including 4% with a complete response, 28% with a very good partial response, and 20% with a partial response. The median duration of response and progression-free survival were 15.7 and 12.0 months, respectively.
Disclosure: For full disclosures of the study authors, visit haematologica.org.
