Acute myeloid leukemia, NPM1-mutated

Section editor
	Ashwin Kishtagari, MD Vanderbilt University Nashville, TN, USA LinkedIn

Note: these are regimens tested in biomarker-specific populations for patients with NPM1-mutated AML, please see the main AML page for other regimens.

3 regimens on this page 4 variants on this page

Guidelines

"How I Treat"

• 2021: Falini et al. How I diagnose and treat NPM1-mutated AML PubMed

NCCN

• NCCN does not have guidelines at this granular level; please see NCCN Guidelines - Acute Myeloid Leukemia.

Upfront induction therapy

Cytarabine & Etoposide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (AMLSG 15-10)	2011-NR	Phase 3 (C)	ATRA, Cytarabine, Etoposide	Not available

Chemotherapy

• Cytarabine (Ara-C)
• Etoposide (Vepesid)

References

1. AMLSG 15-10: NCT01237808

ICE & ATRA

ICE & ATRA: Idarubicin, Cytarabine, Etoposide, All-Trans Retinoic Acid

Regimen variant #1, 60 or younger

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schlenk et al. 2019 (AMLSG 09-09)	2010-2017	Phase 3 (C)	ICE, ATRA, GO	Did not meet primary endpoint of EFS

Chemotherapy

• Idarubicin (Idamycin) as follows:
  • Cycle 1: 12 mg/m² IV once per day on days 1, 3, 5
  • Cycle 2: 12 mg/m² IV once per day on days 1 & 3
• Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose per cycle: 700 mg/m²)
• Etoposide (Vepesid) as follows:
  • Cycle 1: 100 mg/m² IV once per day on days 1 to 3
  • Cycle 2: 100 mg/m² IV once per day on days 1 & 3

Targeted therapy

• All-trans retinoic acid (ATRA) 45 mg/m²/day PO on days 6 to 8, then 15 mg/m²/day PO on days 9 to 21

2 cycles

Subsequent treatment

• HiDAC & ATRA consolidation

Regimen variant #2, older than 60

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schlenk et al. 2019 (AMLSG 09-09)	2010-2017	Phase 3 (C)	ICE, ATRA, GO	Did not meet primary endpoint of EFS

Chemotherapy

• Idarubicin (Idamycin) 12 mg/m² IV once per day on days 1 & 3
• Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose per cycle: 700 mg/m²)
• Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 & 3

Targeted therapy

• All-trans retinoic acid (ATRA) 45 mg/m²/day PO on days 6 to 8, then 15 mg/m²/day PO on days 9 to 21

2 cycles

Subsequent treatment

• HiDAC & ATRA consolidation

References

1. AMLSG 09-09: Schlenk RF, Paschka P, Krzykalla J, Weber D, Kapp-Schwoerer S, Gaidzik VI, Leis C, Fiedler W, Kindler T, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Horst HA, Koller E, Wulf G, Schleicher J, Bentz M, Greil R, Hertenstein B, Krauter J, Martens U, Nachbaur D, Abu Samra M, Girschikofsky M, Basara N, Benner A, Thol F, Heuser M, Ganser A, Döhner K, Döhner H. Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study. J Clin Oncol. 2020 Feb 20;38(6):623-632. Epub 2019 Dec 18. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00893399