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Crenolanib plus intensive chemotherapy for the treatment of FLT3-mutated AML
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The addition of a tyrosine kinase inhibitor (TKI) after standard induction and consolidation therapy is the recommended treatment for young adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML).1 Crenolanib is a second-generation FLT3 inhibitor with activity against both FLT3-ITD and FLT3-TKD, it also has a shorter half-life compared with quizartinib and midostaurin.1
Recently, Wang et al.1 published results from a pilot study (NCT02283177) in Journal of Clinical Oncology investigating crenolanib in combination with intensive chemotherapy for the treatment of young adults with FLT3-ITD and/or TKD mutant newly diagnosed AML. Here, we summarize the key results.
Study design1
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Patients received 7 + 3 (cytarabine and either daunorubicin or idarubicin) induction and high-dose cytarabine consolidation therapy for 2–4 cycles.
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After each induction and consolidation cycle, patients were given 100 mg crenolanib thrice daily, beginning 24 hours after chemotherapy until 72 hours prior to the next chemotherapy.
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The primary endpoint was the safety and tolerability of crenolanib.
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The secondary endpoints were overall response rate, event-free survival, and overall survival.
Key findings1
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A total of 44 patients received crenolanib plus intensive chemotherapy between March 2015 and December 2019.
Safety
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All patients experienced ≥1 adverse event (AE).
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The most frequent treatment-emergent AEs were:
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diarrhea (65.9%);
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nausea (56.8%);
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febrile neutropenia (52.3%);
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vomiting (45.5%); and
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peripheral edema (40.9%).
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Serious AEs occurred in 68% of patients, the most frequent of which was febrile neutropenia (50%).
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A total of seven patients required dose reduction and three patients discontinued treatment due to toxicities.
Efficacy
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Overall, 86% of patients achieved complete response (CR)/CR with incomplete count recovery, with rates comparable between patients aged ≤60 and >60 years (Table 1).
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In patients who achieved a CR/CR with incomplete count recovery, the cumulative incidence of relapse was 31.5%.
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A higher proportion of patients aged ≤ 60 years achieved a negative measurable residual disease CR vs patients aged > 60 years (Table 1).
Table 1. Efficacy endpoints for crenolanib in combination with intensive chemotherapy for the treatment of young adults with newly diagnosed FLT3-mutated AML*
|
Efficacy endpoints, % (unless otherwise stated) |
Patients aged ≤60 years |
Patients aged >60 years |
All patients |
|---|---|---|---|
|
CR/CRi |
90 |
80 |
86 |
|
CR |
76 |
80 |
77 |
|
CRi |
14 |
0 |
9 |
|
Median OS, months |
Not reached |
19.8 |
Not reached |
|
Estimated OS rate |
|
|
|
|
1-year |
78.9 |
66.7 |
74.6 |
|
2-year |
78.9 |
46.7 |
67.6 |
|
3-year |
71.4 |
33.3 |
58.0 |
|
Median EFS, months |
Not reached |
7.9 |
44.7 |
|
MRD negative CR† |
89 |
45 |
72 |
|
FLT3 MRD negative CR‡ |
878 |
73 |
81 |
|
CR, complete response; CRi, CR with incomplete count recovery; EFS, event-free survival; MRD, measurable residual disease; OS, overall survival. |
|||
|
Key learnings |
|---|
|
- Wang E, Goldberg A, Martin T, et al. Crenolanib and intensive chemotherapy in adults with newly diagnosed FLT3-mutated AML. J Clin Oncol. 2024. Online ahead of print. DOI: 10.1200/JCO.23.0106
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