Subcutaneous Daratumumab vs IV Formulation in Relapsed Multiple Myeloma

A subcutaneous formulation of the monoclonal antibody daratumumab proved non-inferior to the intravenous form of daratumumab for patients with relapsed or refractory multiple myeloma, according to topline results of the phase III COLUMBA study.

The study randomly assigned 522 adults with relapsed or refractory multiple myeloma to either subcutaneous daratumumab or intravenous daratumumab until disease progression, unacceptable toxicity, or end of the study. The co-primary endpoints were overall response rate and maximum trough of daratumumab.

Overall response rates were similar between the two formulations, with a rate of 41.1% for the subcutaneous formulation compared with 37.1% for the intravenous formulation. The lower limit of the 95% CI for the ratio of the two met the specified non-inferiority criterion for the co-primary endpoint.

According to data from Genmab, the geometric mean of the C_trough for patients treated with subcutaneous daratumumab was 499 mg/mL compared with 463 mg/mL in patients treated with intravenous daratumumab. Again, the lower limit of the 95% CI for the ratio of the two met the specified non-inferiority criterion for the co-primary endpoint.

Results from COLUMBA showed no new safety signals for daratumumab, and Janssen Biotech, which licensed daratumumab from Genmab in 2012, plans on discussing regulatory submission for this subcutaneous formulation with health authorities.

Phase Ib results of another study of subcutaneous daratumumab were presented at the 2018 American Society of Hematology (ASH) Annual Meeting. The study tested administration of subcutaneous daratumumab in 25 patients with relapsed or refractory disease and found that the subcutaneous administration allowed for dosing in 3 to 5 minutes and improved patient convenience. At 6.5 months’ median follow-up, the overall response rate was 52%.

Daratumumab is currently approved in its intravenous form in the following ways:

• in combination with bortezomib, melphalan, and prednisone for patients with newly diagnosed myeloma who are ineligible for transplant,

• in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for patients with myeloma treated with at least one prior therapy,

• in combination with pomalidomide and dexamethasone for patients with myeloma with at least two prior therapies,

• and, as a monotherapy for patients with myeloma who have had at least three prior therapies, including a proteasome inhibitor and an immunomodulatory agent.