Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: Results from a multicenter, randomized, phase 2/3 study Journal Article
| Authors: | Montesinos, P.; Roboz, G. J.; Bulabois, C. E.; Subklewe, M.; Platzbecker, U.; Ofran, Y.; Papayannidis, C.; Wierzbowska, A.; Shin, H. J.; Doronin, V.; Deneberg, S.; Yeh, S. P.; Ozcan, M. A.; Knapper, S.; Cortes, J.; Pollyea, D. A.; Ossenkoppele, G.; Giralt, S.; Döhner, H.; Heuser, M.; Xiu, L.; Singh, I.; Huang, F.; Larsen, J. S.; Wei, A. H. |
| Article Title: | Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: Results from a multicenter, randomized, phase 2/3 study |
| Abstract: | Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018. Part A confirmed the RP2D of talacotuzumab to be 9 mg/kg. In Part B, CR was achieved in 12/80 (15%) patients receiving combination therapy and in 9/82 (11%) patients receiving decitabine alone (odds ratio: 1.4; 95% confidence interval [CI]: 0.6–3.6; p = 0.44). Median (95% CI) OS was 5.36 (4.27–7.95) months for combination therapy versus 7.26 (6.47–8.64) months for decitabine alone (hazard ratio: 1.04; 95% CI: 0.79–1.37; p = 0.78). Combination therapy showed no improvement in efficacy versus decitabine alone, resulting in the Independent Data Monitoring Committee’s recommendation of early termination of enrollment and discontinuation of talacotuzumab treatment. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | adult; controlled study; treatment response; aged; major clinical study; overall survival; constipation; fatigue; neutropenia; diarrhea; drug efficacy; drug safety; drug withdrawal; monotherapy; recommended drug dose; treatment duration; multiple cycle treatment; phase 2 clinical trial; anemia; nausea; randomized controlled trial; thrombocytopenia; asthenia; chill; dyspnea; febrile neutropenia; fever; pneumonia; hypokalemia; multicenter study; peripheral edema; therapy effect; phase 1 clinical trial; treatment withdrawal; acute myeloid leukemia; decitabine; human; male; female; priority journal; article; talacotuzumab |
| Journal Title: | Leukemia |
| Volume: | 35 |
| Issue: | 1 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-01-01 |
| Start Page: | 62 |
| End Page: | 74 |
| Language: | English |
| DOI: | 10.1038/s41375-020-0773-5 |
| PUBMED: | 32203138 |
| PROVIDER: | scopus |
| PMCID: | PMC7787975 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
