Table 4.

Dose interruption, reduction and discontinuation recommendations for midostaurin in patients with advanced SM.²⁸

Criteria	Dosing
ANC <1.0 × 109/l attributed to midostaurin in patients without MCL, or ANC <0.5 × 109/l in patients with baseline ANC of 0.5–1.5 × 109/l.	Interrupt until ANC ≥1.0 × 109/l, then resume at 50 mg BID and, if tolerated, increase to 100 mg BID. Discontinue if low ANC persists for >21 days and is suspected to be related to midostaurin.
Platelet count <50 × 109/l attributed to midostaurin in patients without MCL, or platelet count <25 × 109/l attributed to midostaurin in patients with baseline platelet count of 25–75 × 109/l.	Interrupt until platelet count ≥50 × 109/l, then resume at 50 mg BID and, if tolerated, increase to 100 mg BID. Discontinue if low platelet count persists for >21 days and is suspected to be related to midostaurin.
Hemoglobin <8 g/dl attributed to midostaurin in patients without MCL, or life-threatening anemia attributed to midostaurin in patients with baseline hemoglobin of 8–10 g/dl.	Interrupt until hemoglobin ≥8 g/dl, then resume at 50 mg BID and, if tolerated, increase to 100 mg BID. Discontinue if low hemoglobin persists for >21 days and is suspected to be related to midostaurin.
Grade 3/4 nausea and/or vomiting despite optimal anti-emetic therapy.	Interrupt for 3 days (6 doses), then resume at 50 mg BID and, if tolerated, gradually increase to 100 mg BID.
Other Grade 3/4 non-hematological toxicities.	Interrupt until event has resolved to Grade ≤2, then resume at 50 mg BID and, if tolerated, increase to 100 mg BID. Discontinue if toxicity is not resolved to Grade ≤2 within 21 days or severe toxicity recurs at a reduced dose.

ANC, absolute neutrophil count; MCL, mast cell leukemia.