Compared with treatment with intravenous daratumumab (DARA IV), subcutaneous daratumumab (DARA SC) demonstrated similar efficacy, with fewer infusion-related reactions (IRRs) in patients with relapsed/refractory (R/R) multiple myeloma (MM), in addition to a reduced treatment burden due to a considerably shorter median administration duration of 5 minutes. These findings come from an update of the phase 3 COLUMBA trial after 13.7 months of median follow-up (6.2 months after the primary analysis), presented by Saad Z. Usmani, MD, from Levine Cancer Institute/Atrium Health in Charlotte, NC.
Daratumumab is a human immunoglobulin G κ light chain monoclonal antibody targeting CD38, and is currently approved for intravenous (IV) administration as a single agent or in combination with standard-of-care regimens for the treatment of MM. A subcutaneous formulation of daratumumab, co-formulated with recombinant human hyaluronidase PH20, was developed to reduce the duration of treatment administration without compromising its safety or efficacy.
The randomized, international, open-label, noninferiority phase 3 COLUMBA study evaluated the efficacy, pharmacokinetics, and safety of DARA SC versus DARA IV in patients with heavily pretreated R/R MM. After a median follow-up of 7.5 months, the study met the coprimary end points of overall response rate (ORR) and maximum trough concentration, and these data were previously reported.
“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 IRR rates,” said Dr Usmani. “DARA SC patients also reported higher treatment satisfaction.”
DARA SC (1800 mg DARA + rHuPH20 [2000 U/mL]), given by manual push over 3 to 5 minutes at alternating left/right abdominal sites, and DARA IV (16 mg/kg IV infusion) were both given in 28-day cycles.
Eligible patients had ≥3 prior lines of therapy, or were double refractory. Coprimary end points were ORR and maximum daratumumab trough concentration. Secondary end points included rates of IRRs, progression-free survival, very good partial response or better (≥VGPR) and complete response or better (≥CR).
A total of 522 patients with a median age of 67 years were randomized 1:1 to either DARA SC (n = 263) or DARA IV (n = 259). Patients in the study had received a median of 4 prior lines of therapy, and all had been previously treated with both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). The majority (82.2%) of patients were refractory to their last line of prior therapy, and about half were refractory to both PIs and IMiDs. At baseline, 26.3% and 17.3% of patients had a high-risk cytogenetic abnormality in the DARA SC and DARA IV groups, respectively.
After a median follow-up of more than 13 months, ORR was improved from 41.1% to 43.3% for DARA SC and from 37.1% to 39.4% for DARA IV. ORRs were comparable between DARA SC and DARA IV across all subgroups, including body weight (median baseline body weight was 73 kg). Noninferiority of ORR for DARA SC (43.3%) versus DARA IV (39.4%) was maintained with longer follow-up.
Median duration of treatment was 6 months in both groups. Rates of deep responses (≥VGPR, ≥CR) were similar between DARA SC and DARA IV, and response rates deepened over time.
Progression-free survival (PFS) and overall survival (OS) were comparable between the groups. Median PFS was 5.6 months with DARA SC versus 6.1 months with DARA IV (P = .9710), and the 12-month PFS rates were 27.2% and 28% with DARA SC and DARA IV, respectively. Median OS was not reached in either arm, and 12-month OS rates were 73.5% and 72.1% with DARA SC and DARA IV, respectively.
Grade 3/4 treatment-related adverse events occurred in 49% of patients in the DARA SC group and 52% of patients in the DARA IV group, but a significantly lower rate of IRRs was observed in patients who received DARA SC (12.7% vs 34.5%). Most IRRs were mild, with few grade 3 events, and none were grade 4 or 5. DARA SC patients were also more satisfied with their cancer therapy than DARA IV patients, according to a modified version of the Cancer Therapy Satisfaction Questionnaire. At the time of data cutoff, 118 patients (evenly distributed across both arms) continued treatment on the study.
“Collectively, the data demonstrate a favorable benefit/risk profile for the use of an 1800-mg flat dose of DARA SC,” Dr Usmani reported.
Usmani S, et al. ASH Abstract 1865. Session 653.