TY - JOUR
TI - Ixazomib as postinduction maintenance for patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplantation: The phase III TOURMALINE-MM4 trial
AU - Dimopoulos, M.A.
AU - Špička, I.
AU - Quach, H.
AU - Oriol, A.
AU - Hájek, R.
AU - Garg, M.
AU - Beksac, M.
AU - Bringhen, S.
AU - Katodritou, E.
AU - Chng, W.-J.
AU - Leleu, X.
AU - Iida, S.
AU - Mateos, M.-V.
AU - Morgan, G.
AU - Vorog, A.
AU - Labotka, R.
AU - Wang, B.
AU - Palumbo, A.
AU - Lonial, S.
AU - TOURMALINE-MM4 study group
JO - Journal of Clinical Oncology
PY - 2020
VL - 38
TODO - 34
SP - 4030-4041
PB - American Society of Clinical Oncology
SN - 0732-183X, 1527-7755
TODO - 10.1200/JCO.20.02060
TODO - antivirus agent;  bortezomib;  cyclophosphamide;  dexamethasone;  immunomodulating agent;  ixazomib;  lenalidomide;  melphalan;  placebo;  prednisone;  proteasome inhibitor;  thalidomide;  antineoplastic agent;  boron derivative;  glycine;  ixazomib;  proteasome inhibitor, adult;  aged;  arthralgia;  Article;  backache;  controlled study;  diarrhea;  double blind procedure;  drug dose reduction;  drug efficacy;  drug safety;  drug withdrawal;  fatigue;  female;  fever;  follow up;  health care quality;  heart arrhythmia;  heart failure;  heart infarction;  herpes zoster;  human;  hypotension;  kidney disease;  liver disease;  maintenance therapy;  major clinical study;  male;  malignant neoplasm;  multiple cycle treatment;  multiple myeloma;  nausea;  neutropenia;  peripheral neuropathy;  phase 3 clinical trial;  pneumonia;  priority journal;  progression free survival;  randomized controlled trial;  rash;  thrombocytopenia;  upper respiratory tract infection;  vomiting;  clinical trial;  maintenance chemotherapy;  middle aged;  multiple myeloma;  stem cell transplantation;  treatment outcome, Aged;  Antineoplastic Agents;  Boron Compounds;  Double-Blind Method;  Female;  Glycine;  Humans;  Maintenance Chemotherapy;  Male;  Middle Aged;  Multiple Myeloma;  Placebos;  Progression-Free Survival;  Proteasome Inhibitors;  Stem Cell Transplantation;  Treatment Outcome
TODO - PURPOSE Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed. PATIENTS AND METHODS The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization. RESULTS Patients were randomly assigned to receive ixazomib (n 5 425) or placebo (n 5 281). TOURMALINEMM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P,.001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P,.001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade $ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%. CONCLUSION Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population. © 2020 by American Society of Clinical Oncology
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