Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib

Autores de IIS La Fe

• Pau Montesinos Fernández

  Autor

Participantes ajenos a IIS La Fe

• Ashaye A.
• Shi L.
• Aldoss I.
• Vachhani P.
• Rocha V.
• Papayannidis C.
• Leonard J.T.
• Baer M.R.
• Ribera J.-M.
• McCloskey J.
• Wang J.
• Rane D.
• Guo S.

Grupos

• Hematología y Hemoterapia

Abstract

Background: In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach. Methods: Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up). Q-TWiST was calculated as the sum of health utility-weighted restricted mean durations of the three states. A relative Q-TWiST gain of = 10% was considered clinically important. Sensitivity analyses were conducted by varying TOX and REL utilities, follow-up time, and the TOX definition (using grade 2+ TEAEs or patient-perceived treatment tolerability assessed by the FACT-GP5). Results: Among all randomized patients (ponatinib n = 164, imatinib n = 81), restricted mean OS was similar between arms (1082.2 vs. 1024.8 days; p = 0.373). In the base-case analysis, mean TWiST was 214.5 days longer with ponatinib versus imatinib (95% CI 70.3–358.7; p = 0.004), REL was shorter by 175.9 days (325.4–26.5; p = 0.021), and TOX was not significantly different between arms (p = 0.228). The relative Q-TWiST gain (10.98%) was clinically important. Sensitivity analyses consistently supported the robustness of the base-case findings. Conclusion: Ponatinib may prolong quality-adjusted survival compared with imatinib, supporting the benefit–risk profile of ponatinib as a front-line treatment for Ph+ ALL. Trial Registration: NCT03589326. © 2025 Takeda Pharmaceuticals USA, Inc. Cancer Medicine published by John Wiley & Sons Ltd.

Keywords

• Adult; Aged; Antineoplastic Agents; Female; Humans; Imatinib Mesylate; Imidazoles; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyridazines; Quality-Adjusted Life Years; Young Adult; imatinib; ponatinib; antineoplastic agent; imatinib; imidazole derivative; ponatinib; pyridazine derivative; acute lymphoblastic leukemia; adult; Article; bone marrow; disease exacerbation; female; follow up; health status; hematopoietic stem cell transplantation; human; major clinical study; male; multiple cycle treatment; outcome assessment; overall survival; patient-reported outcome; phase 3 clinical trial; Philadelphia 1 chromosome; post hoc analysis; progression free survival; quality of life; aged; B cell acute lymphoblastic leukemia; clinical trial; comparative study; controlled study; drug therapy; middle aged; mortality; multicenter study; Philadelphia 1 chromosome; quality adjusted life year; randomized controlled trial; young adult