Table 2.

Glasdegib dose reduction in case of non-hematological toxicities

Toxicity	Glasdegib dosage modification
Non-hematologic toxicities grade ≥3 according to CTCAE criteria (excluding QTc prolongation, muscle spasms, and myalgias). First episode Second episode Third episode	Interrupt medication until toxicity recovers to grade ≤1, then: Dose level decrease 1 (DLD1): 75 mg DLD2: 50 mg Discontinue medication permanently
Renal toxicity, where serum creatinine or BUN are ≥2 × ULN or serum bicarbonate level is < 20 mmol/L. First episode Second episode Third episode	Interrupt medication until toxicity recovers tograde ≤1 then: DLD1 DLD2 Discontinue medication permanently
Electrocardiogram QT corrected (QTc) prolongation grade 1.	Continue at the same level.
QTc prolongation grade 2 and 3.	Interrupt and resume when QTc returns to ≤470 ms: - Within 7 days, dosing as before - Within 14 days, DLD1 Discontinue medication permanently, in case of no return to ≤470 ms after 14 days,
QTc prolongation grade 4 or repetitive grade 3 or grade 2 after DLD1.	Discontinue medication permanently

Toxicity is graded according to CTCAE criteria. Once the Glasdegib dose has been reduced, all subsequent cycles should be administered at that dose level, unless further dose reduction is required. Dose re-escalation is not allowed. Nausea, vomiting, or diarrhea must persist until next therapy cycle at grade ≥3 to require dose modification

Abbreviations: CTCAE Common Terminology Criteria for Adverse Events, QTc QT corrected, DLD1 dose level decrease 1: 75 mg, DLD2 dose level decrease 2: 50 mg, ULN upper limit normal