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

TL;DR

Ponatinib provides better quality-adjusted survival than imatinib in newly diagnosed Philadelphia chromosome-positive ALL patients.

Contribution

This study introduces a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis to compare ponatinib and imatinib in Ph+ ALL.

Findings

Ponatinib extended TWiST by 214.5 days compared to imatinib.

The relative Q-TWiST gain of 10.98% was clinically significant.

Sensitivity analyses confirmed the robustness of the results.

Abstract

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.

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).

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.

Ponatinib may prolong quality‐adjusted survival compared with imatinib, supporting the benefit–risk profile of ponatinib as a front‐line treatment for Ph+ ALL.

NCT03589326

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