Τίτλος:
Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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/d [20 mg/d in patients aged ≥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 cutoff, 13 (11.9%) of 109 and 15 (27.3%) of 55 patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy end point) 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 = .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 or higher 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. Key Points: • In myeloma patients with a median 4 prior therapy lines, adding dexamethasone to isatuximab increased response rates from 23.9% to 43.6%. • Dexamethasone improved isatuximab efficacy with no detrimental effect on safety, supporting the use of this combination regimen. © 2021 American Society of Hematology
Συγγραφείς:
Dimopoulos, M.
Bringhen, S.
Anttila, P.
Capra, M.
Cavo, M.
Cole, C.
Gasparetto, C.
Hungria, V.
Jenner, M.
Vorobyev, V.
Ruiz, E.Y.
Yin, J.Y.
Saleem, R.
Hellet, M.
Macé, S.
Paiva, B.
Vij, R.
Περιοδικό:
Blood advances
Λέξεις-κλειδιά:
ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1; alkylating agent; bortezomib; carfilzomib; CD16 antigen; CD3 antigen; CD56 antigen; cyt 38f 2; daratumumab; dexamethasone; diphenhydramine; Fc receptor; immunoglobulin A; immunoglobulin G; isatuximab; lenalidomide; M protein; methylprednisolone; paracetamol; pomalidomide; ranitidine; antineoplastic agent; immunological antineoplastic agent; isatuximab; monoclonal antibody; thalidomide, adult; adverse drug reaction; aged; arthralgia; Article; asthenia; backache; bone pain; bronchitis; cancer patient; cancer recurrence; cancer staging; cancer survival; chill; clinical evaluation; constipation; controlled study; coughing; decreased appetite; diarrhea; disease exacerbation; drug dose increase; drug efficacy; drug safety; drug withdrawal; dyspepsia; dyspnea; fatigue; fever; gastrointestinal disease; headache; human; immunomodulation; incidence; infestation; infusion related reaction; insomnia; limb pain; major clinical study; mediastinum disease; mental disease; metabolic disorder; monotherapy; multicenter study; multiple cycle treatment; multiple myeloma; musculoskeletal chest pain; musculoskeletal pain; myalgia; nausea; neurologic disease; nose obstruction; nutritional disorder; outcome assessment; overall response rate; overall survival; pain; peripheral edema; phase 1 clinical trial; phase 2 clinical trial; pneumonia; priority journal; progression free survival; randomized controlled trial; respiratory tract infection; rhinopharyngitis; thorax disease; treatment duration; treatment response; upper respiratory tract infection; urinary tract infection; vomiting; clinical trial; female; male; middle aged; multiple myeloma; treatment outcome; tumor recurrence; very elderly, Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Progression-Free Survival; Thalidomide; Treatment Outcome
DOI:
10.1182/blood.2020008209