TY - JOUR
TI - Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma
AU - Dimopoulos, M.
AU - Bringhen, S.
AU - Anttila, P.
AU - Capra, M.
AU - Cavo, M.
AU - Cole, C.
AU - Gasparetto, C.
AU - Hungria, V.
AU - Jenner, M.
AU - Vorobyev, V.
AU - Ruiz, E.Y.
AU - Yin, J.Y.
AU - Saleem, R.
AU - Hellet, M.
AU - Macé, S.
AU - Paiva, B.
AU - Vij, R.
JO - Blood advances
PY - 2021
VL - 137
TODO - 9
SP - 1154-1165
PB - Elsevier B.V.
SN - null
TODO - 10.1182/blood.2020008209
TODO - 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
TODO - 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
ER -