Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome
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Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. / Cortes, Jorge E; Heidel, Florian H; Hellmann, Andrzej; Fiedler, Walter; Smith, B Douglas; Robak, Tadeusz; Montesinos, Pau; Pollyea, Daniel A; DesJardins, Pierre; Ottmann, Oliver; Ma, Weidong Wendy; Shaik, M Naveed; Laird, A Douglas; Zeremski, Mirjana; O'Connell, Ashleigh; Chan, Geoffrey; Heuser, Michael.
In: LEUKEMIA, Vol. 33, No. 2, 02.2019, p. 379-389.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome
AU - Cortes, Jorge E
AU - Heidel, Florian H
AU - Hellmann, Andrzej
AU - Fiedler, Walter
AU - Smith, B Douglas
AU - Robak, Tadeusz
AU - Montesinos, Pau
AU - Pollyea, Daniel A
AU - DesJardins, Pierre
AU - Ottmann, Oliver
AU - Ma, Weidong Wendy
AU - Shaik, M Naveed
AU - Laird, A Douglas
AU - Zeremski, Mirjana
AU - O'Connell, Ashleigh
AU - Chan, Geoffrey
AU - Heuser, Michael
PY - 2019/2
Y1 - 2019/2
N2 - Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC. The primary endpoint was overall survival. Eighty-eight and 44 patients were randomized to glasdegib/LDAC and LDAC, respectively. Median (80% confidence interval [CI]) overall survival was 8.8 (6.9-9.9) months with glasdegib/LDAC and 4.9 (3.5-6.0) months with LDAC (hazard ratio, 0.51; 80% CI, 0.39-0.67, P = 0.0004). Fifteen (17.0%) and 1 (2.3%) patients in the glasdegib/LDAC and LDAC arms, respectively, achieved complete remission (P < 0.05). Nonhematologic grade 3/4 all-causality adverse events included pneumonia (16.7%) and fatigue (14.3%) with glasdegib/LDAC and pneumonia (14.6%) with LDAC. Clinical efficacy was evident across patients with diverse mutational profiles. Glasdegib plus LDAC has a favorable benefit-risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy.
AB - Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC. The primary endpoint was overall survival. Eighty-eight and 44 patients were randomized to glasdegib/LDAC and LDAC, respectively. Median (80% confidence interval [CI]) overall survival was 8.8 (6.9-9.9) months with glasdegib/LDAC and 4.9 (3.5-6.0) months with LDAC (hazard ratio, 0.51; 80% CI, 0.39-0.67, P = 0.0004). Fifteen (17.0%) and 1 (2.3%) patients in the glasdegib/LDAC and LDAC arms, respectively, achieved complete remission (P < 0.05). Nonhematologic grade 3/4 all-causality adverse events included pneumonia (16.7%) and fatigue (14.3%) with glasdegib/LDAC and pneumonia (14.6%) with LDAC. Clinical efficacy was evident across patients with diverse mutational profiles. Glasdegib plus LDAC has a favorable benefit-risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy.
KW - Journal Article
U2 - 10.1038/s41375-018-0312-9
DO - 10.1038/s41375-018-0312-9
M3 - SCORING: Journal article
C2 - 30555165
VL - 33
SP - 379
EP - 389
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 2
ER -