TY - JOUR
T1 - Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined with Azacitidine in Patients with Previously Untreated AML
T2 - Phase Ib Results
AU - Daver, Naval G.
AU - Vyas, Paresh
AU - Kambhampati, Suman
AU - Al Malki, Monzr M.
AU - Larson, Richard A.
AU - Asch, Adam S.
AU - Mannis, Gabriel
AU - Chai-Ho, Wanxing
AU - Tanaka, Tiffany N.
AU - Bradley, Terrence J.
AU - Jeyakumar, Deepa
AU - Wang, Eunice S.
AU - Sweet, Kendra
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
AU - Komrokji, Rami
AU - Xing, Guan
AU - Ramsingh, Giridharan
AU - Renard, Camille
AU - Zeidner, Joshua F.
AU - Sallman, David A.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - PURPOSEMagrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479).PATIENTS AND METHODSPatients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR).RESULTSEighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53-mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was-0.9 g/dL (range,-3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53-mutant and wild-type patients were 9.8 months and 18.9 months, respectively.CONCLUSIONMagrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.
AB - PURPOSEMagrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479).PATIENTS AND METHODSPatients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR).RESULTSEighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53-mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was-0.9 g/dL (range,-3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53-mutant and wild-type patients were 9.8 months and 18.9 months, respectively.CONCLUSIONMagrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.
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U2 - 10.1200/JCO.22.02604
DO - 10.1200/JCO.22.02604
M3 - Article
C2 - 37703506
AN - SCOPUS:85175029722
SN - 0732-183X
VL - 41
SP - 4893
EP - 4904
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 31
ER -