Daratumumab Shows Promise for Systemic Lupus Erythematosus Treatment

Jul 19, 2024

Photo Credit: Sinhyu

Depleting plasma cells with an anti-CD38 antibody led to ameliorations in multiple measures of systemic lupus erythematosus in an open-label phase 2 trial.

Depleting plasma cells with an anti-CD38 antibody led to ameliorations in multiple measures of systemic lupus erythematosus (SLE) in an open-label phase 2 trial. This included decreases in anti-double-stranded (ds) DNA antibody levels from 166.3 U/ml to 61.1 U/ml at week 12.

Dr. Tobias Alexander, MD, reported the results of a single-center, open-label phase 2 study (NCT04810754) that included 10 participants with SLE treated with daratumumab.¹ “The rationale for using daratumumab in lupus was to explore its capacity to deplete plasma cells because we know the plasma cells are implicated in the disease by excreting antibodies,” Dr Alexander explained. The plasma cell-depleting anti-CD38 autoantibody daratumumab is currently approved for multiple myeloma.

All participants had a history of inadequate response to minimally two state-of-the-art immunosuppressants. Inclusion criteria further required an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 4 for clinical features and positive testing for dsDNA antibodies. The participants received 1,800 mg of daratumumab weekly over 8 weeks. The follow-up lasted 36 weeks.

At baseline, median anti-dsDNA antibody levels were 166.3 U/ml, median SLEDAI-2k 12, Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) 6, and Clinical Disease Activity Index (CDAI) 11.5. At week 12, all parameters had changed significantly: the primary endpoint of anti-dsDNA antibody to 61.1 U/ml (P=0.002), and the secondary endpoints of SLEDAI-2k, CLASI, and CDAI to 4 (P=0.002), 0 (P=0.002), and 0 (P=0.004), respectively. Also, IgG levels decreased, and complement C3 levels rose. Prednisolone was reduced from 6.25 mg/day at baseline to 5.0 mg at the final visit, and the SLE Responder Index 4 went from 100% at week 12 to 70% at week 24.

All participants had adverse events, but the safety reports saw no severe adverse events, and the overall safety profile was seen as favorable. “These data support the notion that plasma cells, in addition to B cells, are an attractive target in lupus,” Dr. Alexander concluded.