Year: 2025
Type: conference-abstract
Abstract: 6510 Background: The phase 3 PhALLCON trial (NCT03589326) in adults with newly diagnosed Ph+ ALL met its primary endpoint, showing a significantly higher rate of minimal residual disease negativity (MRDneg; BCR::ABL1 IS ≤0.01%) with complete remission (CR) at end of induction (EOI) with ponatinib (PON) vs imatinib (IMA; 34.4% vs 16.7%; P =0.002) and safety comparable to IMA. We report post hoc analyses of patients (pts) who did not reach MRDneg by EOI. Methods: Pts were randomized 2:1 to PON (30 mg QD reduced to 15 mg upon MRDneg CR at EOI) or IMA (600 mg QD) plus 20 cycles (C) of reduced-intensity chemotherapy (induction C1–3; consolidation C4–9; maintenance combination C10–20) then PON/IMA monotherapy until disease progression or unacceptable toxicity. Cumulative molecular response rates, event-free survival (EFS; defined as any-cause death, no CR by EOI, or relapse from CR), and safety were evaluated in pts with BCR::ABL1 p190/p210 confirmed by central lab at baseline who did not reach MRDneg by EOI and those achieving MRDneg post-cycle 4 day 1 (C4D1). Data cutoff: Aug 12, 2022. Results: Of 232 pts (PON/IMA: n=154/78) with p190/p210, 140 (86 [56%]/54 [69%]) did not have MRDneg by EOI (median age: 54 y; ≥60 y: 37%; female: 55%; ECOG 0/1: 44%/49%; p190/p210: 66%/34%). Of these, 113 pts (PON/IMA: 73/40) continued treatment after EOI, 48 of whom (35 [48%]/13 [33%]) reached MRDneg (MR4 or better) post-C4D1 (Table). Of those 48 pts (median age: 54 y; ≥60 y: 33%; female: 60%; ECOG 0/1: 46%/54%; p190/p210: 71%/29%), median duration of MRDneg (95% CI) was not reached (NR; 13.0 mo–NR) with PON and 3.8 mo (2.3–NR) with IMA; 16 pts (PON/IMA: 10/6) had HSCT. In the 140 pts without MRDneg by EOI, median EFS (mEFS; 95% CI) was NR (NR–NR) with PON and 24.8 mo (21.3–NR) with IMA; 2-y EFS (95% CI) was 82% (69–90) and 62% (41–77), respectively. In the 48 pts with MRDneg post-C4D1, mEFS was NR (NR–NR) and NR (21.3 mo–NR); 2-y EFS was 88% (68–96) and 80% (20–97), respectively. In the 140 pts without MRDneg by EOI, treatment-emergent adverse event (TEAE) rates with PON/IMA were 100%/98% (gr ≥3: 91%/94%); dose modification due to TEAEs: 71%/54% (discontinuation: 15%/9%; reduction: 16%/28%; interruption: 66%/41%). In the 48 pts with MRDneg post-C4D1, TEAE rates with PON/IMA were 100%/100% (gr ≥3: 91%/100%); dose modification due to TEAEs: 69%/62% (discontinuation: 6%/0%; reduction: 11%/46%; interruption: 69%/38%). Conclusions: Among pts without MRDneg by EOI, more pts who continued the study achieved deep and durable molecular response after C4D1, and 2-y EFS appeared to be better with PON than IMA. These data support the clinical benefit and tolerability of continuing PON in pts without MRDneg by EOI. Clinical trial information: NCT03589326 . Response in pts without MRDneg by EOI who continued treatment post-C4D1, n (%) PON (n=73) IMA (n=40) MRDneg 35 (48) 13 (33) By end of C9 28 (38) 11 (28) By end of C20 30 (41) 12 (30) MR4.5 ( BCR :: ABL1 IS ≤0.0032%) 27 (37) 4 (10) By end of C9 17 (23) 2 (5) By end of C20 23 (32) 3 (8)
Source: Journal of Clinical Oncology
Authors: Ibrahim Aldoss, Pankit Vachhani, Hagop M. Kantarjian, Pau Montesinos, Jessica Taft Leonard, David Gomez-Almaguer, Maria R. Baer, Carlo Gambacorti-Passerini, James K. McCloskey, Yosuke Minami, Cristina Papayannidis, Vanderson Geraldo Rocha, Philippe Rousselot, Eunice S. Wang, Lin Yang, Meliessa Hennessy, Alexander Vorog, Niti Patel, Jose-Maria Ribera-Santasusana, Elias Jabbour
Institutions: City Of Hope National Medical Center, City of Hope, University of Alabama at Birmingham, The University of Texas MD Anderson Cancer Center, Hospital Universitari i Politècnic La Fe, Oregon Health & Science University, Universidad Autónoma de Nuevo León, Hospital Universitario Dr José Eleuterio Gonzalez, University of Maryland, Baltimore, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Milano-Bicocca, Hackensack University Medical Center, National Cancer Center Hospital East, Istituto di Ematologia di Bologna, University of Bologna, Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, Université de Versailles Saint-Quentin-en-Yvelines, Roswell Park Comprehensive Cancer Center, Hospital Universitari Germans Trias i Pujol
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410809604