Difference between revisions of "Acute myeloid leukemia, NPM1-mutated"
Jump to navigation
Jump to search
Warner-admin (talk | contribs) m (Text replacement - "</big>" to "") |
Warner-admin (talk | contribs) m (Text replacement - "'''dosing details in manuscript have been reviewed'''" to "'''dosing details in manuscript have been reviewed by our editors'''") |
||
(One intermediate revision by the same user not shown) | |||
Line 83: | Line 83: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''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. [https://doi.org/10.1200/JCO.19.01406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ link to PMC article] ''' | + | # '''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. [https://doi.org/10.1200/JCO.19.01406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31851556/ PubMed] [https://clinicaltrials.gov/study/NCT00893399 NCT00893399] |
##'''Update:''' Döhner H, Weber D, Krzykalla J, Fiedler W, Kühn MWM, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Döhner K, Ganser A; German–Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. Epub 2023 May 12. [https://doi.org/10.1016/s2352-3026(23)00089-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37187198/ PubMed] | ##'''Update:''' Döhner H, Weber D, Krzykalla J, Fiedler W, Kühn MWM, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Döhner K, Ganser A; German–Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. Epub 2023 May 12. [https://doi.org/10.1016/s2352-3026(23)00089-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37187198/ PubMed] | ||
Line 114: | Line 114: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''AMLSG 15-10:''' Schlenk RF, Weber D, Krzykalla J, Kindler T, Wulf G, Hertenstein B, Salih HR, Südhoff T, Krauter J, Martens U, Wessendorf S, Runde V, Tischler HJ, Bentz M, Koller E, Heuser M, Thol F, Benner A, Ganser A, Döhner K, Döhner H. Randomized phase-III study of low-dose cytarabine and etoposide + /- all-trans retinoic acid in older unfit patients with NPM1-mutated acute myeloid leukemia. Sci Rep. 2023 Sep 8;13(1):14809. [https://doi.org/10.1038/s41598-023-41964-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10491626/ link to PMC article] ''' | + | #'''AMLSG 15-10:''' Schlenk RF, Weber D, Krzykalla J, Kindler T, Wulf G, Hertenstein B, Salih HR, Südhoff T, Krauter J, Martens U, Wessendorf S, Runde V, Tischler HJ, Bentz M, Koller E, Heuser M, Thol F, Benner A, Ganser A, Döhner K, Döhner H. Randomized phase-III study of low-dose cytarabine and etoposide + /- all-trans retinoic acid in older unfit patients with NPM1-mutated acute myeloid leukemia. Sci Rep. 2023 Sep 8;13(1):14809. [https://doi.org/10.1038/s41598-023-41964-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10491626/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37684299/ PubMed] [https://clinicaltrials.gov/study/NCT01237808 NCT01237808] |
=Consolidation after upfront therapy= | =Consolidation after upfront therapy= | ||
Line 146: | Line 146: | ||
'''3 cycles''' | '''3 cycles''' | ||
===References=== | ===References=== | ||
− | # '''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. [https://doi.org/10.1200/JCO.19.01406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ link to PMC article] ''' | + | # '''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. [https://doi.org/10.1200/JCO.19.01406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31851556/ PubMed] [https://clinicaltrials.gov/study/NCT00893399 NCT00893399] |
##'''Update:''' Döhner H, Weber D, Krzykalla J, Fiedler W, Kühn MWM, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Döhner K, Ganser A; German–Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. Epub 2023 May 12. [https://doi.org/10.1016/s2352-3026(23)00089-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37187198/ PubMed] | ##'''Update:''' Döhner H, Weber D, Krzykalla J, Fiedler W, Kühn MWM, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Döhner K, Ganser A; German–Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. Epub 2023 May 12. [https://doi.org/10.1016/s2352-3026(23)00089-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37187198/ PubMed] | ||
[[Category:Acute myeloid leukemia regimens]] | [[Category:Acute myeloid leukemia regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Acute leukemias]] | [[Category:Acute leukemias]] |
Latest revision as of 12:21, 15 July 2024
Section editor | |
---|---|
Ashwin Kishtagari, MD Vanderbilt University Nashville, TN, USA |
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
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Acute Myeloid Leukemia.
Upfront induction therapy
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 | Might have inferior EFS61 (co-primary endpoint) |
1Reported efficacy is based on the 2023 update.
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 | Might have inferior EFS61 (co-primary endpoint) |
1Reported efficacy is based on the 2023 update.
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
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00893399
- Update: Döhner H, Weber D, Krzykalla J, Fiedler W, Kühn MWM, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Döhner K, Ganser A; German–Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. Epub 2023 May 12. link to original article PubMed
First-line induction therapy, older or "unfit" patients
Note: these regimens are generally considered to be part of a non-curative line of treatment.
Cytarabine & Etoposide (CYVE)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schlenk et al. 2023 (AMLSG 15-10) | 2011-05-11 to 2016-09-14 | Phase 3 (C) | ATRA, Cytarabine, Etoposide | Seems to have superior OS (primary endpoint) |
Chemotherapy
- Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 7
- Etoposide (Vepesid) as follows:
- Cycle 1: 50 mg/m2 PO or IV once per day on days 1 to 3
- Cycle 2 to 6: 100 mg/m2 PO or IV once per day on days 1 to 3
28-day cycle for 6 cycles
References
- AMLSG 15-10: Schlenk RF, Weber D, Krzykalla J, Kindler T, Wulf G, Hertenstein B, Salih HR, Südhoff T, Krauter J, Martens U, Wessendorf S, Runde V, Tischler HJ, Bentz M, Koller E, Heuser M, Thol F, Benner A, Ganser A, Döhner K, Döhner H. Randomized phase-III study of low-dose cytarabine and etoposide + /- all-trans retinoic acid in older unfit patients with NPM1-mutated acute myeloid leukemia. Sci Rep. 2023 Sep 8;13(1):14809. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01237808
Consolidation after upfront therapy
HiDAC & ATRA
HiDAC & ATRA: High Dose Ara-C (Cytarabine) & All-Trans Retinoic Acid
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Schlenk et al. 2019 (AMLSG 09-09) | 2010-2017 | Non-randomized part of phase 3 RCT |
Preceding treatment
- ICE & ATRA induction
Chemotherapy
- Cytarabine (Ara-C) by the following age-based criteria:
- 18 to 60 years old: 3000 mg/m2 IV every 12 hours on days 1 to 3 (6 doses total)
- Older than 60 years old: 1000 mg/m2 IV every 12 hours on days 1 to 3 (6 doses total)
Targeted therapy
- All-trans retinoic acid (ATRA) 15 mg/m2 PO once per day on days 4 to 21
Supportive therapy
- Pegfilgrastim (Neulasta) 6 mg SC once on day 8
3 cycles
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00893399
- Update: Döhner H, Weber D, Krzykalla J, Fiedler W, Kühn MWM, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Döhner K, Ganser A; German–Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. Epub 2023 May 12. link to original article PubMed