PMID- 33914097 OWN - NLM STAT- MEDLINE DCOM- 20210526 LR - 20210526 IS - 1432-0584 (Electronic) IS - 0939-5555 (Linking) VI - 100 IP - 6 DP - 2021 Jun TI - A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients. PG - 1497-1508 LID - 10.1007/s00277-021-04542-8 [doi] AB - Prognosis for relapsed or refractory (R/R) acute myeloid leukemia (AML) despite salvage therapy is dismal. This phase I dose-escalation trial assessed the safety and preliminary clinical activity of selinexor, an oral exportin-1 (XPO1) inhibitor, in combination with FLAG-Ida in younger R/R AML patients. The aim was to find the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD). Fourteen patients were included, and selinexor dosage was 60 mg (3 patients), 80 mg (3 patients), and 100 mg (7 patients) weekly. No dose-limiting toxicities were reported. Grade >/=3 non-hematologic adverse events (AEs) occurred in 78.6% of patients. Two patients were non MTD evaluable due to early death, and overall, 3 out of 14 patients (21.4%) had fatal AEs. Five out of 12 (42%) response and MTD evaluable patients achieved a complete remission (CR; n=4) or CR with incomplete hematologic recovery (CRi, n=1), and 4 patients (33%) subsequently underwent allogeneic transplantation. The median overall survival (OS) and event-free survival (EFS) were 6.0 (range 0.9-19.3) and 1.1 months (range 0.7-19.3), respectively. Using selinexor 100 mg/weekly, CR/CRi rate of 66.7%, OS 13.6 months (range, 1.6-19.3), and EFS 10.6 months (range, 0.9-19.3). At last follow-up, 3 patients were alive. Selinexor 100 mg/weekly with FLAG-Ida combination in R/R AML showed acceptable tolerability and efficacy, establishing the RP2D of this regimen in future clinical trials. ClinicalTrials.gov Identifier: NCT03661515. FAU - Martinez Sanchez, Maria P AU - Martinez Sanchez MP AD - Servicio de Hematologia y Hemoterapia, Hospital Universitario 12 de Octubre, UCM, CNIO, CIBERONC, Madrid, Spain. FAU - Megias-Vericat, Juan Eduardo AU - Megias-Vericat JE AUID- ORCID: 0000-0002-0369-5341 AD - Servicio de Farmacia, Area del Medicamento, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Rodriguez-Veiga, Rebeca AU - Rodriguez-Veiga R AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Vives, Susana AU - Vives S AD - Servicio de Hematologia y Hemoterapia, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain. FAU - Bergua, Juan Miguel AU - Bergua JM AD - Servicio de Hematologia y Hemoterapia, Hospital San Pedro de Alcantara, Caceres, Spain. FAU - Torrent, Anna AU - Torrent A AD - Servicio de Hematologia y Hemoterapia, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain. FAU - Suarez-Varela, Sara AU - Suarez-Varela S AD - Servicio de Hematologia y Hemoterapia, Hospital San Pedro de Alcantara, Caceres, Spain. FAU - Boluda, Blanca AU - Boluda B AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Martinez-Lopez, Joaquin AU - Martinez-Lopez J AD - Servicio de Hematologia y Hemoterapia, Hospital Universitario 12 de Octubre, UCM, CNIO, CIBERONC, Madrid, Spain. FAU - Cano-Ferri, Isabel AU - Cano-Ferri I AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Acuna-Cruz, Evelyn AU - Acuna-Cruz E AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Torres-Minana, Laura AU - Torres-Minana L AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Martin-Herreros, Beatriz AU - Martin-Herreros B AD - Grupo de investigacion en Hematologia, Instituto de Investigacion Sanitaria La Fe (IISLAFE), Valencia, Spain. FAU - Serrano, Alfons AU - Serrano A AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Sempere, Amparo AU - Sempere A AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Barragan, Eva AU - Barragan E AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Sargas, Claudia AU - Sargas C AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Sanz, Miguel AU - Sanz M AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Martinez-Cuadron, David AU - Martinez-Cuadron D AUID- ORCID: 0000-0001-7540-4091 AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. FAU - Montesinos, Pau AU - Montesinos P AUID- ORCID: 0000-0002-3275-5593 AD - Servicio de Hematologia y Hemoterapia, Hospital Universitari i Politecnic La Fe, Valencia, Spain. montesinos_pau@gva.es. CN - PETHEMA group LA - eng SI - ClinicalTrials.gov/NCT03661515 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study DEP - 20210429 PL - Germany TA - Ann Hematol JT - Annals of hematology JID - 9107334 RN - 0 (Hydrazines) RN - 0 (Triazoles) RN - 04079A1RDZ (Cytarabine) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 31TZ62FO8F (selinexor) RN - FA2DM6879K (Vidarabine) RN - ZRP63D75JW (Idarubicin) RN - Ida-FLAG protocol SB - IM MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects/*therapeutic use MH - Cytarabine/administration & dosage/adverse effects/therapeutic use MH - Granulocyte Colony-Stimulating Factor/administration & dosage/adverse effects/therapeutic use MH - Humans MH - Hydrazines/administration & dosage/adverse effects/*therapeutic use MH - Idarubicin/administration & dosage/adverse effects/therapeutic use MH - Leukemia, Myeloid, Acute/*drug therapy MH - Male MH - Maximum Tolerated Dose MH - Middle Aged MH - Neoplasm Recurrence, Local/*drug therapy MH - Treatment Outcome MH - Triazoles/administration & dosage/adverse effects/*therapeutic use MH - Vidarabine/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use OTO - NOTNLM OT - AML OT - FLAG-Ida OT - KPT-330 OT - Relapsed/refractory OT - Selinexor OT - XPO1 EDAT- 2021/04/30 06:00 MHDA- 2021/05/27 06:00 CRDT- 2021/04/29 12:28 PHST- 2021/03/12 00:00 [received] PHST- 2021/04/19 00:00 [accepted] PHST- 2021/04/30 06:00 [pubmed] PHST- 2021/05/27 06:00 [medline] PHST- 2021/04/29 12:28 [entrez] AID - 10.1007/s00277-021-04542-8 [pii] AID - 10.1007/s00277-021-04542-8 [doi] PST - ppublish SO - Ann Hematol. 2021 Jun;100(6):1497-1508. doi: 10.1007/s00277-021-04542-8. Epub 2021 Apr 29.