Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study
<p><strong>Purpose:</strong> Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society of Clinical Oncology
2023
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| _version_ | 1824458885421858816 |
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| author | Sallman, DA Al Malki, MM Asch, AS Wang, ES Jurcic, JG Bradley, TJ Flinn, IW Pollyea, DA Kambhampati, S Tanaka, TN Zeidner, JF Garcia-Manero, G Jeyakumar, D Komrokji, R Lancet, J Kantarjian, HM Gu, L Zhang, Y Tan, A Chao, M O'Hear, C Ramsingh, G Lal, I Vyas, P Daver, NG |
| author_facet | Sallman, DA Al Malki, MM Asch, AS Wang, ES Jurcic, JG Bradley, TJ Flinn, IW Pollyea, DA Kambhampati, S Tanaka, TN Zeidner, JF Garcia-Manero, G Jeyakumar, D Komrokji, R Lancet, J Kantarjian, HM Gu, L Zhang, Y Tan, A Chao, M O'Hear, C Ramsingh, G Lal, I Vyas, P Daver, NG |
| author_sort | Sallman, DA |
| collection | OXFORD |
| description | <p><strong>Purpose:</strong> Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479).</p>
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<p><strong>Patients and Methods:</strong> Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once‐weekly or once‐every-2-week maintenance dose. 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 complete remission (CR) rate.</p>
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<p><strong>Results:</strong> Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was −0.7 g/dL (range, −3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53-mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS.</p>
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<p><strong>Conclusion:</strong> Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).</p> |
| first_indexed | 2025-02-19T04:33:00Z |
| format | Journal article |
| id | oxford-uuid:55419707-43d9-48d7-a71c-18e90cc9fa4c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:33:00Z |
| publishDate | 2023 |
| publisher | American Society of Clinical Oncology |
| record_format | dspace |
| spelling | oxford-uuid:55419707-43d9-48d7-a71c-18e90cc9fa4c2025-01-21T09:36:25ZMagrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:55419707-43d9-48d7-a71c-18e90cc9fa4cEnglishSymplectic ElementsAmerican Society of Clinical Oncology2023Sallman, DAAl Malki, MMAsch, ASWang, ESJurcic, JGBradley, TJFlinn, IWPollyea, DAKambhampati, STanaka, TNZeidner, JFGarcia-Manero, GJeyakumar, DKomrokji, RLancet, JKantarjian, HMGu, LZhang, YTan, AChao, MO'Hear, CRamsingh, GLal, IVyas, PDaver, NG<p><strong>Purpose:</strong> Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479).</p> <br> <p><strong>Patients and Methods:</strong> Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once‐weekly or once‐every-2-week maintenance dose. 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 complete remission (CR) rate.</p> <br> <p><strong>Results:</strong> Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was −0.7 g/dL (range, −3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53-mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS.</p> <br> <p><strong>Conclusion:</strong> Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).</p> |
| spellingShingle | Sallman, DA Al Malki, MM Asch, AS Wang, ES Jurcic, JG Bradley, TJ Flinn, IW Pollyea, DA Kambhampati, S Tanaka, TN Zeidner, JF Garcia-Manero, G Jeyakumar, D Komrokji, R Lancet, J Kantarjian, HM Gu, L Zhang, Y Tan, A Chao, M O'Hear, C Ramsingh, G Lal, I Vyas, P Daver, NG Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study |
| title | Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study |
| title_full | Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study |
| title_fullStr | Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study |
| title_full_unstemmed | Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study |
| title_short | Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study |
| title_sort | magrolimab in combination with azacitidine in patients with higher risk myelodysplastic syndromes final results of a phase ib study |
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