All-Oral Treatment of Newly Diagnosed Acute Myeloid Leukemia

• p. 1 Abstract, Results

  Common adverse events of grade 3 or higher in phase 2b were anemia (in 30% of the patients), neutropenia (in 26%)

• p. 8 Table 3, Most frequent treatment-related adverse events, phase 2b grade ≥3

  30 (30)

Only the authors can say what is right here.

Judge's note: Table 3 (p8) lists events by term only under 'Most frequent treatment-related adverse events'. The phase 2b grade ≥3 rates there are anemia 30 (30), neutropenia 26 (26) and febrile neutropenia 25 (25). The abstract (p1) does not say 'treatment-related', and the paper gives no all-cause rates by term. This is a labelling ambiguity, not a wrong number.

Second check: another model agreed

• p. 3 End Points and Assessments, first sentence

  The trial had pharmacokinetic (phases 1 and 2a) and efficacy (phase 2b) end points.

• p. 3 End Points and Assessments, phase 2a

  on days 5 and 15 of cycle 2 and complete response

• p. 1 Abstract, Methods

  complete response (phase 2a–b)

Judge's note: On p3, the opening sentence of End Points assigns efficacy to phase 2b only. Further down the same page, the phase 2a primary end points are venetoclax AUC/Cmax 'and complete response', and the phase 2a secondary end points are efficacy end points. The two statements are inconsistent.

Second check: another model agreed

• p. 2 Methods, Trial Design and Patients

  on a 5-point scale in which higher scores reflect greater disability

• p. 5 Table 1 footnote †

  performance-status scores range from 0 to 5

Judge's note: Checked p2 Methods and the Table 1 footnote † on p5. A 0–5 range has six points, so the two descriptions of the same scale disagree.

Second check: another model agreed

• p. 3 End Points and Assessments

  with or without decitabine–cedazuridine on days 5 and 15 of cycle 2

• p. 4 Statistical Analysis

  decitabine–cedazuridine pharmacokinetic data from previous studies as the comparator

• p. 6 Pharmacokinetic Results

  historical data on venetoclax alone

Only the authors can say what is right here.

Judge's note: On p3, the End Points section gives the venetoclax AUC/Cmax end point with or without DEC-C on cycle 2 days 5 and 15. On p4, Statistical Analysis says 'venetoclax alone' for the venetoclax comparison and 'decitabine–cedazuridine pharmacokinetic data from previous studies as the comparator' only for decitabine. On p5–6, the PK Results say the combined phase 1–2a exposure 'was similar to that with historical data on venetoclax alone'. No passage explains a historical venetoclax comparator. Only the authors can say which comparator was used.

Second check: another model agreed

• p. 3 End Points, phase 2b secondary end points

  on day 5 with venetoclax in cycles 1, 2, and 3

• p. 4 Methods, bioanalysis

  cycle 1 day 5 and cycle 2 day 3 (phase 2b). For phase 2b, blood samples were also collected on cycle 3 day 3.

Only the authors can say what is right here.

Judge's note: Checked p3 (End Points) and p4 (bioanalysis). The end-point days and the sampling days differ for cycles 2 and 3. Figure 1A allows DEC-C on days 1–3 in later cycles, which may explain day-3 sampling, but the end-point definition was not updated to match.

Second check: another model agreed

• p. 7 Results, efficacy/OS paragraph

  fewer patients were receiving 28 days of venetoclax or 5 days of decitabine–cedazuridine with progressive treatment cycles

• p. 3 Figure 1C

  100 98 100 80 86 80 94 68 72 81 42 65

Judge's note: Read the Figure 1B and 1C bar labels on p3. Every series falls steadily across cycles except phase 1 DEC-C, which goes 100, 80, 94, 81. The reviewer's remark about phase 2b venetoclax rising is wrong: the values are 45, 29, 15, 12, a steady fall. The statement holds as a general trend, so this is a minor wording point.

Second check: another model agreed

• p. 5 Results, Patients

  Approximately 25% of the patients in all groups had adverse cytogenetics.

• p. 5 Table 1, Adverse cytogenetics

  5 (17)

Judge's note: Checked Table 1 and the Results text on p5. The phase 2a and 2b values are near 25%, but the phase 1 value of 17% is not, so 'all groups' overstates.

Second check: another model agreed

• p. 7 Results, Safety

  grade 3 or 4 myelosuppression: anemia (26%), neutropenia (21%), febrile neutropenia (21%), and thrombocytopenia (14%)

• p. 8 Table 3, Platelet count decreased / Neutrophil count decreased grade ≥3

  11 (37)

• p. 7

  anemia (26%), neutropenia (21%), febrile neutropenia (21%), and thrombocytopenia (14%)

Judge's note: The pooled percentages in the text match Table 3 (p8): anemia 49/189, neutropenia 40/189, febrile neutropenia 39/189, thrombocytopenia 27/189. The laboratory terms in Table 3 are more frequent but are not listed. The authors may have meant clinical terms only, but the text does not say so. Reviewer note 2's comparison with the abstract is not valid: the abstract gives phase 2b-only values, a different population.

Second check: another model agreed

• p. 2 Trial Design and Regimens

  venetoclax at dose of 400 mg daily

Judge's note: The p2 image, Trial Design and Regimens, shows 'venetoclax at dose of 400 mg daily' as printed.

Second check: none (judge only)

• p. 10 Reference 15

  The 2024 Rrevision to the Decla-ration of Helsinki

• p. 10 Reference 15

  The 2024 Rrevision to the Decla-

Judge's note: The crop of the p10 reference list shows 'Rrevision' as printed, so this is not an extraction artefact.

Second check: none (judge only)