Abstract
FLT3-ITD-mutated acute myeloid leukemia (AML) remains a therapeutic challenge. FLT3 inhibition in the setting of minimal residual disease and a new immune system via allogeneic transplantation offers a promise of improved survival for these patients. We performed a prospective study of patients with FLT3-ITD AML undergoing allogeneic transplant that was conducted to evaluate the safety, tolerability, and outcome of sorafenib administered peritransplant. Sorafenib dosing was individualized, starting at 200 mg twice a day (BID), and titrated based on tolerability or toxicities until a tolerable dose was identified. Forty-four patients, with a median age of 52 years, undergoing allogeneic transplant were started on sorafenib in the peritransplant period (21 pretransplant). The median duration of post-transplant follow-up was 27.6 months (range, 5.2 to 60.4). Overall survival was 76% at both 24 and 36 months. Event-free survival at 24 and 36 months was 74% and 64%, respectively. Ten patients died in the post-transplant period, with 6 deaths due to relapsed leukemia and 4 from transplant-associated toxicity. Tolerable doses ranged from 200 mg every other day to 400 mg BID with similar exposure. Correlative studies evaluating FLT3 inhibition via a plasma inhibitory activity assay showed consistent inhibition of FLT3 at all tolerability-determined dosing levels. Sorafenib is well tolerated in the peritransplant setting irrespective of the conditioning intensity or the donor source. Our findings indicate that sorafenib dosing can be individualized in the post-transplantation setting according to patient tolerability. This approach results in effective in vivo FLT3 inhibition and yields encouraging survival results.
| Original language | English (US) |
|---|---|
| Journal | Biology of Blood and Marrow Transplantation |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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Keywords
- FLT3
- Maintenance
- Post-transplant
ASJC Scopus subject areas
- Hematology
- Transplantation
Cite this
A Prospective Study of Peritransplant Sorafenib for Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Transplantation. / ETCTN-8922 study team.
In: Biology of Blood and Marrow Transplantation, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Prospective Study of Peritransplant Sorafenib for Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Transplantation
AU - ETCTN-8922 study team
AU - Pratz, Keith W.
AU - Rudek, Michelle A.
AU - Smith, B. Douglas
AU - Karp, Judith
AU - Gojo, Ivana
AU - Dezern, Amy
AU - Jones, Richard J.
AU - Greer, Jackie
AU - Gocke, Christopher
AU - Baer, Maria R.
AU - Duong, Vu H.
AU - Rosner, Gary
AU - Zahurak, Marianna
AU - Wright, John J.
AU - Emadi, Ashkan
AU - Levis, Mark
PY - 2019/1/1
Y1 - 2019/1/1
N2 - FLT3-ITD-mutated acute myeloid leukemia (AML) remains a therapeutic challenge. FLT3 inhibition in the setting of minimal residual disease and a new immune system via allogeneic transplantation offers a promise of improved survival for these patients. We performed a prospective study of patients with FLT3-ITD AML undergoing allogeneic transplant that was conducted to evaluate the safety, tolerability, and outcome of sorafenib administered peritransplant. Sorafenib dosing was individualized, starting at 200 mg twice a day (BID), and titrated based on tolerability or toxicities until a tolerable dose was identified. Forty-four patients, with a median age of 52 years, undergoing allogeneic transplant were started on sorafenib in the peritransplant period (21 pretransplant). The median duration of post-transplant follow-up was 27.6 months (range, 5.2 to 60.4). Overall survival was 76% at both 24 and 36 months. Event-free survival at 24 and 36 months was 74% and 64%, respectively. Ten patients died in the post-transplant period, with 6 deaths due to relapsed leukemia and 4 from transplant-associated toxicity. Tolerable doses ranged from 200 mg every other day to 400 mg BID with similar exposure. Correlative studies evaluating FLT3 inhibition via a plasma inhibitory activity assay showed consistent inhibition of FLT3 at all tolerability-determined dosing levels. Sorafenib is well tolerated in the peritransplant setting irrespective of the conditioning intensity or the donor source. Our findings indicate that sorafenib dosing can be individualized in the post-transplantation setting according to patient tolerability. This approach results in effective in vivo FLT3 inhibition and yields encouraging survival results.
AB - FLT3-ITD-mutated acute myeloid leukemia (AML) remains a therapeutic challenge. FLT3 inhibition in the setting of minimal residual disease and a new immune system via allogeneic transplantation offers a promise of improved survival for these patients. We performed a prospective study of patients with FLT3-ITD AML undergoing allogeneic transplant that was conducted to evaluate the safety, tolerability, and outcome of sorafenib administered peritransplant. Sorafenib dosing was individualized, starting at 200 mg twice a day (BID), and titrated based on tolerability or toxicities until a tolerable dose was identified. Forty-four patients, with a median age of 52 years, undergoing allogeneic transplant were started on sorafenib in the peritransplant period (21 pretransplant). The median duration of post-transplant follow-up was 27.6 months (range, 5.2 to 60.4). Overall survival was 76% at both 24 and 36 months. Event-free survival at 24 and 36 months was 74% and 64%, respectively. Ten patients died in the post-transplant period, with 6 deaths due to relapsed leukemia and 4 from transplant-associated toxicity. Tolerable doses ranged from 200 mg every other day to 400 mg BID with similar exposure. Correlative studies evaluating FLT3 inhibition via a plasma inhibitory activity assay showed consistent inhibition of FLT3 at all tolerability-determined dosing levels. Sorafenib is well tolerated in the peritransplant setting irrespective of the conditioning intensity or the donor source. Our findings indicate that sorafenib dosing can be individualized in the post-transplantation setting according to patient tolerability. This approach results in effective in vivo FLT3 inhibition and yields encouraging survival results.
KW - FLT3
KW - Maintenance
KW - Post-transplant
UR - http://www.scopus.com/inward/record.url?scp=85074472273&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074472273&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.09.023
DO - 10.1016/j.bbmt.2019.09.023
M3 - Article
C2 - 31550496
AN - SCOPUS:85074472273
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
ER -