Subcutaneous (SC) daratumumab is preferred over intravenous (IV) daratumumab for patients with relapsed or refractory multiple myeloma (MM), according to researchers.

Final results from the phase 3 COLUMBA study showed that SC and IV daratumumab produce similar response and survival outcomes, but SC daratumumab is associated with a lower rate of infusion-related reactions (IRRs) and a shorter administration time (3-5 minutes vs 3-7 hours for IV). Researchers reported these results in Haematologica.

The COLUMBA study (ClinicalTrials.gov Identifier: NCT03277105) included 522 patients with relapsed/refractory MM. The patients were randomly assigned to receive SC daratumumab (1800 mg of daratumumab co-formulated with rHuPH20 at 2000 U/mL; n=263) or IV daratumumab (16 mg/kg of daratumumab; n=259). 


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Daratumumab was administered once weekly for cycles 1-2, once every 2 weeks for cycles 3-6 (all cycles, 28 days), then once every 4 weeks until disease progression or toxicity.

At the final analysis, the overall response rate was 43.7% in the SC group and 39.8% in the IV group. The rate of very good partial response was 23.6% and 21.6%, respectively.

At a median follow-up of 29.3 months, the median progression-free survival was 5.6 months in the SC group and 6.1 months in the IV group (hazard ratio [HR], 0.98; 95% CI, 0.81-1.19). The median overall survival was 28.2 months and 25.6 months, respectively (HR, 0.92; 95% CI, 0.72-1.18).

No new safety signals emerged from the primary analysis to the final analysis. The researchers reported grade 3-4 treatment-emergent adverse events (TEAEs) in 50.8% of patients in the SC group and 52.7% in the IV group. 

The most common grade 3-4 TEAEs (in the SC and IV groups, respectively) were thrombocytopenia (14.2% and 13.6%), anemia (13.8% and 15.1%), and neutropenia (13.1% and 7.8%). 

SC daratumumab produced a lower rate of IRRs than did IV daratumumab. The rate of IRRs was 12.7% in the SC arm and 34.5% in the IV arm. The rate of grade 3-4 IRRs was 1.5% and 5.4%, respectively.

“The final analysis of COLUMBA provides long-term efficacy and tolerability data on daratumumab monotherapy and strongly supports the use of [daratumumab] SC to achieve clinical outcomes comparable to those with [daratumumab] IV, with a low rate of IRR, short administration time, and without dose adjustment,” the researchers wrote. “Based on these results, daratumumab SC is considered a preferable treatment option relative to daratumumab IV for the patients with multiple myeloma.” 

Disclosures: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Usmani SZ, Nahi H, Legiec W, et al. Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. Published online October 1, 2022. doi:10.3324/haematol.2021.279459