Higher levels of treatment satisfaction without compromising efficacy: subcutaneous daratumumab in RRMM

Results of a phase 3 study of daratumumab monotherapy administered subcutaneously (SC) compared with intravenous (IV) administration in patients with relapsed/refractory multiple myeloma (RRMM) showed no significant differences in efficacy or pharmacokinetic endpoints [1].

The IV formulation of daratumumab, a monoclonal antibody targeting CD38, has been approved as either monotherapy or in combination with standard-of-care regimens for patients with RRMM, or when combined with bortezomib/melphalan/dexamethasone for transplant-ineligible, newly diagnosed patients with MM. However, IV daratumumab is typically infused over hours and is associated with infusion reactions in a substantial percentage of patients.

In the open-label, multicentre, phase 3 COLUMBA trial, 522 adult patients with RRMM were randomly assigned in a 1:1 ratio to receive an SC formulation of daratumumab, including recombinant human hyaluronidase to temporarily break down the hyaluronan barrier to allow for the more rapid administration of large volumes of drug. The formulation was a fixed dose of 1,800 mg once weekly in cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks in cycle 7 and beyond, with each cycle lasting 4 weeks, and administered using alternating left/right abdominal site injections. This was compared with the IV formulation (16 mg/kg once weekly in cycle 1 and 2, every 2 weeks in cycle 3 to 6, and every 4 weeks in cycle 7 and beyond).

The co-primary endpoints of the study were overall response rate and the maximum pre-dose trough concentration of daratumumab on day 1 of cycle 3, with both endpoints analysed for noninferiority. Patient characteristics and disease-related characteristics of the study population included a median age of 67 years, a median of 4 previous lines of therapy, as well as prior treatment with both an immunomodulatory drug and a proteasome inhibitor in all patients.

At a median follow-up of 7.5 months, the overall response rates were 41.1% and 37.1% for patients receiving SC and IV formulations, respectively. In addition, the ratio of the maximum pre-dose trough concentration of daratumumab on day 1 of cycle 3 for SC daratumumab over IV daratumumab was 108%. Furthermore, median PFS was 5.6 months vs 6.1 months for patients receiving the SC and IV formulations of daratumumab, respectively (P=0.9258).

Anaemia, neutropenia, thrombocytopenia, and diarrhoea were the most common treatment-emergent adverse events reported in the study. The 2 study arms showed generally comparable safety profiles, although rates of grade 3/4 neutropenia were slightly higher for patients receiving SC daratumumab (13%) compared with IV daratumumab (8%). The rates of treatment discontinuation due to an adverse event were 7% and 8% for those receiving SC and IV daratumumab, respectively. While 34.5% of patients receiving IV daratumumab experienced infusion reactions, these were reported in only 12.7% of those receiving SC daratumumab. Injection-site reactions occurred in approximately 7% of patients receiving SC daratumumab. Importantly, the median duration of injection for SC daratumumab was 5 minutes compared with infusion times of 421 minutes, 255 minutes, and 205 minutes for patients receiving the first, second, and subsequent infusions of IV daratumumab. A striking difference was noted in assessments of treatment satisfaction over time of patients in the 2 study arms, showing higher levels of satisfaction with treatment for patients receiving SC daratumumab compared with IV daratumumab.

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   1. Mateos M-V, et al. Abstract S823, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

 



Posted on 9 August 201918 March 2024