Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma

Abstract

In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) μg/mL for DARA SC and 496 (SD, 231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice. (Clinicaltrials gov. Identifier: NCT03277105.

Figure 1.

Response rates over time. Response rates from the primary COLUMBA analysis (median follow-up, 7.5 months) and the final COLUMBA analysis (median follow-up, 29.3 months) for patients in the intent-to-treat population. Response rates are shown for the DARA SC and DARA IV groups. ORR: overall response rate; VGPR: very good partial response; PR: partial response; DARA SC: daratumumab by subcutaneous administration; DARA IV: daratumumab by intravenous administration; CR: complete response; sCR: stringent complete response.

Figure 2.

Kaplan-Meier estimates for progression-free survival in the intent-to-treat population. Data included all patients who underwent randomization. Estimated 12-month progression-free survival (PFS) rates are shown. DARA SC: daratumumab by subcutaneous administration; DARA IV: daratumumab by intravenous administration; CI: confidence interval.

Figure 3.

Kaplan-Meier estimates for overall survival in the intent-to-treat population. Data included all patients who underwent randomization. Estimated 24-month overall survival (OS) rates are shown. DARA SC: daratumumab by subcutaneous administration; DARA IV: daratumumab by intravenous administration; CI: confidence interval.

Figure 4.

Kaplan-Meier estimates for progression-free survival in the intent-to-treat population. Data included all patients who underwent randomization. PFS2: time from randomization to progression on next line of therapy or death, based on investigator assessment; DARA SC: daratumumab by subcutaneous administration; DARA IV: daratumumab by intravenous administration; CI: confidence interval.

Figure 5.

Plot of mean (standard deviation) daratumumab serum peak and trough concentrations over time. Data represented as mean with error bars denoting standard deviation for patients who received ≥1 administration of study therapy and had ≥1 pharmacokinetics sample concentration value after the first dose administration. C: cycle; D: day; Pre: pre-dose; EOD: end of dose; PK: pharmacokinetics; DARA SC: daratumumab by subcutaneous administration; DARA IV: daratumumab by intravenous administration.