This Phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/day [20 mg/day in patients ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cut-off, 13/109 (11.9%) and 15/55 (27.3%) patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy endpoint) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859, P = 0.008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade ≥3 infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as NCT01084252.
Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma / Meletios A Dimopoulos; Sara Bringhen; Pekka M Anttila; Marcelo Capra; Michele Cavo; Craig Emmitt Cole; Cristina Gasparetto; Vania Tietsche de Moraes Hungria; Matthew W Jenner; Vladimir I. Vorobyev; Eduardo Patricio Yanez Ruiz; Jian Y Yin; Rao Saleem; Maeva Hellet; Sandrine Macé; Bruno Paiva; Ravi Vij. - In: BLOOD. - ISSN 0006-4971. - ELETTRONICO. - 137:9(2021), pp. 1154-1165. [10.1182/blood.2020008209]
Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma
Michele Cavo;
2021
Abstract
This Phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/day [20 mg/day in patients ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cut-off, 13/109 (11.9%) and 15/55 (27.3%) patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy endpoint) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859, P = 0.008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade ≥3 infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as NCT01084252.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.