Subcutaneous Daratumumab Demonstrates Efficacy Similar to IV Formulation, with Fewer Side Effects

In patients with heavily pretreated relapsed or refractory multiple myeloma, subcutaneous daratumumab (DARA SC) demonstrated efficacy similar to the IV formulation (DARA IV), but with fewer infusion-related reactions, according to Saad Z. Usmani, MD, from Levine Cancer Institute/Atrium Health in Charlotte, NC. These findings come from an update of the phase 3 COLUMBA trial presented at the 2019 ASH Annual Meeting.

Patients who received the drug subcutaneously also had a reduced treatment burden due to a considerably shorter median administration duration of about 5 minutes.

“With longer follow-up, safety and efficacy data continue to support that DARA SC and DARA IV have similar safety profiles, with a statistically significant reduction in infusion-related reaction rates,” said Dr Usmani. “DARA SC patients also reported higher treatment satisfaction.”

Daratumumab is currently approved for IV administration as a single agent or in combination with standard-of-care regimens for the treatment of multiple myeloma. A subcutaneous formulation (coformulated with recombinant human hyaluronidase PH20) was developed in the hope of reducing patients’ duration of treatment administration without compromising safety or efficacy.

This international, open-label noninferiority trial met its coprimary end points of overall response rate (ORR) and maximum trough concentration after a median follow-up of 7.5 months, and these data were previously reported. At ASH, Dr Usmani presented updated findings after a median follow-up of almost 14 months.

Both formulations of the drug were given in 28-day cycles: DARA SC (1800 mg DARA + rHuPH20 [2000 U/mL]) was given by manual push over 3 to 5 minutes at alternating left/right abdominal sites, and DARA IV was given at a dose of 16 mg/kg.

Eligible patients had 3 or more prior lines of therapy and were double refractory. A total of 522 patients with a median age of 67 years and a median of 4 prior lines of therapy were randomly assigned to either DARA SC (n = 263) or DARA IV (n = 259). At baseline, 26.3% of DARA SC patients and 17.3% of DARA IV patients had a high-risk cytogenetic abnormality.

All patients had previously been treated with both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), the majority (82.2%) were refractory to their last line of therapy, and about half were refractory to both PIs and IMiDs. The median duration of treatment was 6 months in both groups.

After a median follow-up of over 13 months, ORR rose from 41.1% to 43.3% for DARA SC patients, and from 37.1% to 39.4% for patients who received DARA IV. Response rates were comparable between the cohorts and across all important subgroups, including body weight.

With longer follow-up, the noninferiority of ORR for DARA SC (43.3%) versus DARA IV (39.4%) was maintained, the investigators reported.

Rates of deep responses (very good partial response or better; complete response or better) were similar between the groups, and response rates deepened over time. Median progression-free survival and median overall survival were also comparable, with no statistically significant differences observed between the groups.

Grade 3/4 treatment-related adverse events occurred in about half of patients in both groups, but at a slightly higher rate in the DARA IV group: 49% versus 52%. Although most infusion-related reactions were mild, they occurred at a significantly lower rate in patients who received DARA SC compared with DARA IV (12.7% vs 34.5%).

Patients who received the subcutaneous formulation were also more satisfied with their cancer treatment than DARA IV patients, according to a modified version of the Cancer Therapy Satisfaction Questionnaire.

“Collectively, the data demonstrate a favorable benefit/risk profile for the use of an 1800-mg flat dose of DARA SC,” Dr Usmani concluded.