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PURPOSE: Magrolimab 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 METHODS: Patients 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). RESULTS: Eighty-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. CONCLUSION: Magrolimab 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

The CLL-IPI is a risk-weighted prognostic model for previously untreated patients with chronic lymphocytic leukemia (CLL), but has not been evaluated in patients with relapsed CLL or on novel therapies. We evaluated the CLL-IPI in 897 patients with relapsed/refractory CLL in 3 randomized trials testing idelalisib (PI3K inhibitor). The CLL-IPI identified patients as low (2.2%), intermediate (12.8%), high (48.7%), and very high (36.2%) risk and was prognostic for survival (log-rank p<.0001; C-statistic 0.706). Of CLL-IPI factors, age >65, 2-microglobulin >3.5mg/L, unmutated immunoglobulin heavy chain variable region gene, and deletion 17p/TP53 mutation were independently prognostic, but Rai I-IV or Binet B/C was not. The CLL-IPI is prognostic for survival in relapsed CLL and with idelalisib therapy. However, low/intermediate risk is uncommon, and regression parameters of individual factors in this risk-weighted model appear different in relapsed CLL. Reassessment of the weighting of the individual variables might optimize the model in this setting.

The CLL-IPI is a risk-weighted prognostic model for previously untreated patients with chronic lymphocytic leukemia (CLL), but has not been evaluated in patients with relapsed CLL or on novel therapies. We evaluated the CLL-IPI in 897 patients with relapsed/refractory CLL in 3 randomized trials testing idelalisib (PI3K inhibitor). The CLL-IPI identified patients as low (2.2%), intermediate (12.8%), high (48.7%), and very high (36.2%) risk and was prognostic for survival (log-rank p<.0001; C-statistic 0.706). Of CLL-IPI factors, age >65, 2-microglobulin >3.5mg/L, unmutated immunoglobulin heavy chain variable region gene, and deletion 17p/TP53 mutation were independently prognostic, but Rai I-IV or Binet B/C was not. The CLL-IPI is prognostic for survival in relapsed CLL and with idelalisib therapy. However, low/intermediate risk is uncommon, and regression parameters of individual factors in this risk-weighted model appear different in relapsed CLL. Reassessment of the weighting of the individual variables might optimize the model in this setting.

The removal is discussed of Sb and Bi from Cu electrolytes by the addition of As. The results are presented of an investigation in which a new type of precipitate, antimony arsantimonate, was observed during precipitation reactions in acidic solution containing As(III), Sb(III) and Sb(V). The As content in the antimony arsantimonate increased with the n(As(III))/n(Sb) ratio in solution, while the content of the Sb(III) and Sb(V) components remained almost constant. The antimony arsantimonate appeared as floccules with sizes of 1-5 micrometres. Crystallisation of the compound improved with a decrease in the n(As(III))/n(Sb) ratio. The precipitate contained As-OH, Sb-OH, As-O-Sb, Sb-O-Sb and O-H chemical bonds. Structural analysis confirmed that purification of the electrolyte occurred as a result of the formation of the antimony arsantimonate precipitate., The removal is discussed of Sb and Bi from Cu electrolytes by the addition of As. The results are presented of an investigation in which a new type of precipitate, antimony arsantimonate, was observed during precipitation reactions in acidic solution containing As(III), Sb(III) and Sb(V). The As content in the antimony arsantimonate increased with the n(As(III))/n(Sb) ratio in solution, while the content of the Sb(III) and Sb(V) components remained almost constant. The antimony arsantimonate appeared as floccules with sizes of 1-5 micrometres. Crystallisation of the compound improved with a decrease in the n(As(III))/n(Sb) ratio. The precipitate contained As-OH, Sb-OH, As-O-Sb, Sb-O-Sb and O-H chemical bonds. Structural analysis confirmed that purification of the electrolyte occurred as a result of the formation of the antimony arsantimonate precipitate.