BLEXIMENIB IN COMBINATION WITH INTENSIVE CHEMOTHERAPY: A PHASE 1B STUDY IN NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA WITH KMT2A OR NPM1 ALTERATIONS

@article{dohner2026bleximenib,
  title = {{BLEXIMENIB IN COMBINATION WITH INTENSIVE CHEMOTHERAPY: A PHASE 1B STUDY IN NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA WITH KMT2A OR NPM1 ALTERATIONS}},
  author = {Hartmut DÖHNER and Andre C SCHUH and Christian RECHER and Jenny O'NIONS and Ibrahim ALDOSS and Ana Alfonso PIÉROLA and Alicia ALLRED and Juan Manuel ALONSO-DOMINGUEZ and Laura BARREYRO and Pierre BORIES and Nikki DASKALAKIS and Matteo G DELLA PORTA and Amber D'SOUZA and James DUGAN and Jordi ESTEVE and Amir T FATHI and Lucille FERRANTE and Stan GAJ and Sylvain GARCIAZ and Ana GARRIDO DIAZ and Olga SALAMERO and Christina GUTTKE and Emmanuel GYAN and Elias JABBOUR and Madlen JENTZSCH and Hagop M KANTARJIAN and Marina KONOPLEVA and Jan KRÖNKE and Marie Luise HüTTER-KRÖNKE and Christina LOEFGREN and Oliver LOMAS and Valentina MANCINI and Ioannis MANTZARIS and Daniel MORILLO and Kathryn PACKMAN and Cristina PAPAYANNIDIS and Ulrike PHILIPPAR and Uwe PLATZBECKER and Sara GARRIDO PANIAGUA and Naa SACKEY and Tim SAUER and Prathap NAGARAJA SHASTRI and Emma SEARLE and Natalia TOVAR and Danielle TRANCUCCI and Nicolas VALLET and Lachlin VAUGHAN and Paresh VYAS and Andrew H WEI and Monserrat ROJAS and Christoph RöLLIG},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107848},
  url = {https://doi.org/10.1016/j.htct.2026.107848},
  note = {CC BY},
}

TY  - JOUR
TI  - BLEXIMENIB IN COMBINATION WITH INTENSIVE CHEMOTHERAPY: A PHASE 1B STUDY IN NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA WITH KMT2A OR NPM1 ALTERATIONS
AU  - Hartmut DÖHNER
AU  - Andre C SCHUH
AU  - Christian RECHER
AU  - Jenny O'NIONS
AU  - Ibrahim ALDOSS
AU  - Ana Alfonso PIÉROLA
AU  - Alicia ALLRED
AU  - Juan Manuel ALONSO-DOMINGUEZ
AU  - Laura BARREYRO
AU  - Pierre BORIES
AU  - Nikki DASKALAKIS
AU  - Matteo G DELLA PORTA
AU  - Amber D'SOUZA
AU  - James DUGAN
AU  - Jordi ESTEVE
AU  - Amir T FATHI
AU  - Lucille FERRANTE
AU  - Stan GAJ
AU  - Sylvain GARCIAZ
AU  - Ana GARRIDO DIAZ
AU  - Olga SALAMERO
AU  - Christina GUTTKE
AU  - Emmanuel GYAN
AU  - Elias JABBOUR
AU  - Madlen JENTZSCH
AU  - Hagop M KANTARJIAN
AU  - Marina KONOPLEVA
AU  - Jan KRÖNKE
AU  - Marie Luise HüTTER-KRÖNKE
AU  - Christina LOEFGREN
AU  - Oliver LOMAS
AU  - Valentina MANCINI
AU  - Ioannis MANTZARIS
AU  - Daniel MORILLO
AU  - Kathryn PACKMAN
AU  - Cristina PAPAYANNIDIS
AU  - Ulrike PHILIPPAR
AU  - Uwe PLATZBECKER
AU  - Sara GARRIDO PANIAGUA
AU  - Naa SACKEY
AU  - Tim SAUER
AU  - Prathap NAGARAJA SHASTRI
AU  - Emma SEARLE
AU  - Natalia TOVAR
AU  - Danielle TRANCUCCI
AU  - Nicolas VALLET
AU  - Lachlin VAUGHAN
AU  - Paresh VYAS
AU  - Andrew H WEI
AU  - Monserrat ROJAS
AU  - Christoph RöLLIG
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107848
UR  - https://doi.org/10.1016/j.htct.2026.107848
AB  - Aim: Bleximenib is a potent, selective menin inhibitor with activity in NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) Previous data have shown an acceptable safety and efficacy profile in participants (pts) with newly diagnosed (ND) NPM1m or KMT2Ar AML treated with Bleximenib (blex) in combination with intensive chemotherapy (IC). We now report updated safety and efficacy data (clinical cut-off: July 2025) from this combination treatment in IC-eligible ND AML pts. Methods: In the Phase 1b ALE1002 study (NCT05453903), Cohort C1 received standard 7+3 induction (cytarabine plus daunorubicin or idarubicin) with blex 30–100 mg BID starting on Day 4 and continued through count recovery. Patients achieving CR received up to 4 consolidation cycles with intermediate-dose cytarabine plus blex; those not undergoing allo-HSCT could continue blex for up to 12 months. The safety population included all patients receiving blex 30–100 mg BID with 7+3. Relative dose intensity (RDI) was defined as received/planned blex dose per 28-day cycle. The ITT efficacy population included all NPM1m or KMT2Ar patients treated with blex 100 mg BID plus 7+3, regardless of study discontinuation before first response assessment. Responses were assessed per ELN criteria. Results: The safety analysis set included 44 ND AML pts median age 57.0 years; 52.3% female; 56.8% NPM1m, 43.2% KMT2A; 15.9% FLT3 co-mutations; ELN risk classification: 44.2% favorable, 27.9% intermediate, 27.9% adverse. The median duration of follow-up was 6.3 months (range, 1.31–22.51). All 44 pts had ≥1 treatment-emergent adverse event (TEAE, all grades), with the most common being thrombocytopenia (79.5%), neutropenia (72.7%), diarrhea (70.5%), nausea (68.2%), anemia, and febrile neutropenia (both 63.6%). The majority of cytopenia TEAEs were Grade 3/4, consistent with an IC backbone. Of the 44 pts, the 30- and 60-day mortality was 0/44 (0%) and 1/44 (2.3%), respectively. There was no differentiation syndrome (DS) observed. Three TEAEs of QT prolongation were reported, all of which were Grade 1/2 and resolved without blex interruption. Among 37 pts achieving composite CR (cCR=CR + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi]), the median time from Day 1 of induction to platelet count recovery was 32.0 days (22.0–82.0), and the median time to neutrophil count recovery was 30.0 days (21.0–71.0). During induction, the median RDI of blex was 100% with no required dose reductions of co-agents. Of 24 pts (NPM1m, n=15; KMT2Ar, n=9) in the ITT efficacy dataset receiving blex 100 mg BID in combination with ‘7+3’, overall response rate (ORR; ≥partial response) was 95.8%, cCR was 87.5%, and CR/CRh was 75%. Responses were similar across mutational subtypes. Median time to CR in the 100 mg BID group was 28 days (range, 21–36) and this was similar to the median time to first response. Median duration of response was not reached. Four pts receiving blex 100 mg BID in combination with ‘7+3’ proceeded to allogenic transplant. Conclusions: In ND NPM1m or KMT2Ar AML, the safety profile of blex + ‘7+3’, including count recovery, was consistent with a ‘7+3’ IC backbone, with no DS adverse events and no QTc prolongation signal observed. Combined with early efficacy, the clinical data are supportive of a planned Phase 3 study blex + ‘7+3’ in IC-eligible ND AML pts harboring KMT2Ar or NPM1m.
SN  - 2531-1379
SN  - 2531-1387
ER  -