Cladribine, High-Dose AraC, Plus Gemtuzumab Ozogamicin (CLAG-GO) As Frontline Intensive Therapy for Fit Patients with Core-Binding Factor Acute Myeloid Leukemia: Preliminary Results

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.2903-2903
• Main Authors: Gener-Ricos, Georgina, Borthakur, Gautam, Sasaki, Koji, Tang, Guilin, Montalban-Bravo, Guillermo, Jabbour, Elias, Ohanian, Maro, Yilmaz, Musa, Haddad, Fadi G., Chien, Kelly S., Ishizawa, Jo, Short, Nicholas J., Maiti, Abhishek, Swaminathan, Mahesh, Garcia-Manero, Guillermo, Daver, Naval, DiNardo, Courtney D., Ravandi, Farhad, Kadia, Tapan M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-187795

Background: Core-binding factor (CBF) acute myeloid leukemias (AML) are associated with favorable outcomes when treated with intensive therapy regimens, particularly based on high-dose cytarabine. In addition, gemtuzumab-ozogamicin (GO) added to frontline chemotherapy showed improved survival in patients with CBF-AML in a meta-analysis of five randomized trials (Hills RK, et all. 2014). Since then, GO has been incorporated to the intensive regimen [traditional ‘3+7‘ or fludarabine-cytarabine and GCSF (FLAG)] and has become the standard approach for CBF-AML. Methods: Fit patients with newly diagnosed AML with inv(16) or t(16;16), CBFB::MYH11 [AML -inv(16)] and AML with t(8;21), RUNX1::RUNX1T1 [AML -t(8;21)] were eligible to receive cladribine, cytarabine, GCSF and GO (CLAG-GO) regimen as frontline intensive chemotherapy. We evaluated baseline patient's characteristics, disease features, and early molecular-response dynamics, including qPCR for each CBF-AML, along with count recovery after cycle 1 (C1) and 2 (C2). Response criteria were standard as defined by the European Leukemia Net (ELN) 2022. Results: Fifteen patients (pts) diagnose with CBF-AML were included, with a median age 47 years (range, 20 - 66 years), 53% were males. Median WBC were 15.5x10^9/L (range, 2.4 - 103). Eleven pts (73%) had AML -inv(16) and 4 pts (27%) had AML -t(8;21). Nine of 11 AML -inv(16) had a CBFB::MYH11 fusion transcript variant A and 2 of 11 pts had a CBFB::MYH11 fusion transcript variant non-A. Median CBF transcript level by qPCR at diagnose was 54.5% (range, 29.5 - 63.6) for AML -inv(16) and median qPCR of 100% (range, 100 - 100) for AML -t(8;21). Median number of co-mutations was 2 (range, 0 - 5), commonly kinase signaling mutations in components of the RAS/MAPK pathway (Figure 1). All pts received induction therapy with cladribine 5mg/m2 (D1-D5), cytarabine 2g/m2 (D1-D5), GCSF (D1 and D5) and GO 3mg/m2 (D1 or D2). If responses were achieved, subsequent consolidation cycles (up to 6 cycles) could be given with CLAG-GO (CLAG on D1-D3 and GO on D1 of C3 and C5). Thirteen pts (87%) were evaluable after induction therapy. Of the 2 non-evaluable pts, one died during induction, and 1 patient is still receiving induction therapy at the last cut off. All pts (13/13) achieved a complete remission (CR) with full count recovery (complete remission -CR- 100%). Twelve of them had minimal residual disease (MRD) assessed by flow cytometry (FC), and 11/12 (91%) pts achieved MRD negative (