Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma Journal Article
| Authors: | Usmani, S. Z.; Nahi, H.; Legiec, W.; Grosicki, S.; Vorobyev, V.; Spicka, I.; Hungria, V.; Korenkova, S.; Bahlis, N. J.; Flogegard, M.; Bladé, J.; Moreau, P.; Kaiser, M.; Iida, S.; Laubach, J.; Magen, H.; Cavo, M.; Hulin, C.; White, D.; De Stefano, V.; Lantz, K.; O'Rourke, L.; Heuck, C.; Delioukina, M.; Qin, X.; Nnane, I.; Qi, M.; Mateos, M. V. |
| Article Title: | 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. © 2022 Ferrata Storti Foundation Published under a CC BY-NC license. |
| Keywords: | controlled study; treatment outcome; overall survival; drug tolerability; neutropenia; cancer recurrence; drug efficacy; drug safety; follow up; antineoplastic agent; progression free survival; multiple myeloma; neoplasm recurrence, local; anemia; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; maintenance therapy; body weight; dexamethasone; cancer therapy; risk factor; monoclonal antibody; lymphocytopenia; antibodies, monoclonal; immunotherapy; immunoglobulin g; tumor recurrence; immunogenicity; time to maximum plasma concentration; phase 3 clinical trial; toxicity; disease exacerbation; intravenous drug administration; phase 3 clinical trial (topic); overall response rate; administration, intravenous; humans; human; article; disease assessment; daratumumab; target lesion revascularization; iron binding capacity; trough concentration |
| Journal Title: | Haematologica |
| Volume: | 107 |
| Issue: | 10 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2022-10-01 |
| Start Page: | 2408 |
| End Page: | 2417 |
| Language: | English |
| DOI: | 10.3324/haematol.2021.279459 |
| PUBMED: | 35354247 |
| PROVIDER: | scopus |
| PMCID: | PMC9521240 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2023 -- Source: Scopus |
