Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: A randomized, open-label, multicenter, phase 2 study (CENTAURUS) Journal Article
| Authors: | Landgren, C. O.; Chari, A.; Cohen, Y. C.; Spencer, A.; Voorhees, P.; Estell, J. A.; Sandhu, I.; Jenner, M. W.; Williams, C.; Cavo, M.; van de Donk, N. W. C. J.; Beksac, M.; Moreau, P.; Goldschmidt, H.; Kuppens, S.; Bandekar, R.; Clemens, P. L.; Neff, T.; Heuck, C.; Qi, M.; Hofmeister, C. C. |
| Article Title: | Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: A randomized, open-label, multicenter, phase 2 study (CENTAURUS) |
| Abstract: | Current guidelines for smoldering multiple myeloma (SMM) recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM. In CENTAURUS, 123 patients with intermediate-risk or high-risk SMM were randomly assigned to daratumumab 16 mg/kg intravenously on extended intense (intense), extended intermediate (intermediate), or short dosing schedules. At the prespecified primary analysis (15.8-month median follow-up), the complete response (CR) rates (co-primary endpoint) were 2.4%, 4.9%, and 0% for intense, intermediate, and short dosing, respectively; the co-primary endpoint of CR rate >15% was not met. Progressive disease (PD)/death rates (number of patients who progressed or died divided by total duration of progression-free survival [PFS] in patient-years; co-primary endpoint) for intense, intermediate, and short dosing were 0.055 (80% confidence interval [CI], 0.014–0.096), 0.102 (80% CI, 0.044–0.160), and 0.206 (80% CI, 0.118–0.295), respectively, translating to a median PFS ≥24 months in all arms (P < 0.0001, <0.0001, and =0.0213, respectively). With longer follow-up (median follow-up, 25.9 months), CR rates were 4.9%, 9.8%, and 0% for intense, intermediate, and short dosing, respectively. PD/death rates for intense, intermediate, and short dosing were 0.059 (80% CI, 0.025–0.092), 0.107 (80% CI, 0.058–0.155), and 0.150 (80% CI, 0.089–0.211), respectively, again translating to a median PFS ≥ 24 months in all arms (P < 0.0001 for all arms). Twenty-four–month PFS rates were 89.9% (90% CI, 78.5–95.4%), 82.0% (90% CI, 69.0–89.9%), and 75.3% (90% CI, 61.1–85.0%) for intense, intermediate, and short dosing, respectively. Pharmacokinetic analyses indicated that intense dosing maintained target-saturating trough concentrations in most patients throughout weekly, every-2-week, and every-4-week dosing periods. No new safety signals were observed. These data provide the basis for an ongoing phase 3 study of daratumumab in SMM. © 2020, The Author(s). |
| Keywords: | adult; controlled study; treatment response; survival rate; major clinical study; fatigue; diarrhea; drug efficacy; drug safety; hypertension; monotherapy; side effect; cancer patient; follow up; melanoma; progression free survival; multiple cycle treatment; pain; phase 2 clinical trial; nausea; randomized controlled trial; thrombocytopenia; dehydration; high risk patient; alanine aminotransferase blood level; arthralgia; coughing; dyspnea; hyperglycemia; lymphocytopenia; pneumonia; lung embolism; alanine aminotransferase; hyponatremia; insomnia; depression; heart failure; multicenter study; unstable angina pectoris; sepsis; cataract; open study; asthma; osteoarthritis; flu like syndrome; headache; intestine perforation; embolism; pericardial effusion; ileus; leukocytosis; atrial fibrillation; musculoskeletal disease; hemangioblastoma; hypertriglyceridemia; upper respiratory tract infection; pleurisy; breast disease; abdominal discomfort; hip fracture; anastomosis leakage; hemiplegia; intermediate risk patient; dysarthria; vasculitis; angina pectoris; mortality rate; diverticulitis; infusion related reaction; smoldering multiple myeloma; human; male; female; priority journal; article; daratumumab; elevated blood pressure |
| Journal Title: | Leukemia |
| Volume: | 34 |
| Issue: | 7 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-07-01 |
| Start Page: | 1840 |
| End Page: | 1852 |
| Language: | English |
| DOI: | 10.1038/s41375-020-0718-z |
| PUBMED: | 32024950 |
| PROVIDER: | scopus |
| PMCID: | PMC7326703 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
