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

March 2020 Vol 11, No 3


Multiple Myeloma

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.

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Last modified: August 10, 2023

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