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.

Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma / Usmani S.Z.; Nahi H.; Legiec W.; Grosicki S.; Vorobyev V.; Spicka I.; Hungria V.; Korenkova S.; Bahlis N.J.; Flogegard M.; Blade 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.. - In: HAEMATOLOGICA. - ISSN 0390-6078. - STAMPA. - 107:10(2022), pp. 2408-2417. [10.3324/haematol.2021.279459]

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

Cavo M.;
2022

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
Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma / Usmani S.Z.; Nahi H.; Legiec W.; Grosicki S.; Vorobyev V.; Spicka I.; Hungria V.; Korenkova S.; Bahlis N.J.; Flogegard M.; Blade 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.. - In: HAEMATOLOGICA. - ISSN 0390-6078. - STAMPA. - 107:10(2022), pp. 2408-2417. [10.3324/haematol.2021.279459]
Usmani S.Z.; Nahi H.; Legiec W.; Grosicki S.; Vorobyev V.; Spicka I.; Hungria V.; Korenkova S.; Bahlis N.J.; Flogegard M.; Blade 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/897511
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