MRD negativity after end of induction in the phase 3 PhALLCON trial: A post hoc analysis.

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)