TY - JOUR
T1 - Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy
T2 - results from a multicenter, randomized, phase 2/3 study
AU - Montesinos, Pau
AU - Roboz, Gail J.
AU - Bulabois, Claude Eric
AU - Subklewe, Marion
AU - Platzbecker, Uwe
AU - Ofran, Yishai
AU - Papayannidis, Cristina
AU - Wierzbowska, Agnieszka
AU - Shin, Ho Jin
AU - Doronin, Vadim
AU - Deneberg, Stefan
AU - Yeh, Su Peng
AU - Ozcan, Mehmet Ali
AU - Knapper, Steven
AU - Cortes, Jorge
AU - Pollyea, Daniel A.
AU - Ossenkoppele, Gert
AU - Giralt, Sergio
AU - Döhner, Hartmut
AU - Heuser, Michael
AU - Xiu, Liang
AU - Singh, Indrajeet
AU - Huang, Fei
AU - Larsen, Julie S.
AU - Wei, Andrew H.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41375-020-0773-5
DO - 10.1038/s41375-020-0773-5
M3 - Article
C2 - 32203138
AN - SCOPUS:85081676423
SN - 0887-6924
VL - 35
SP - 62
EP - 74
JO - Leukemia
JF - Leukemia
IS - 1
ER -
