Impact of clinical response and treatment tolerability on HRQoL in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with ponatinib or imatinib

TL;DR

This study found that ponatinib improves quality of life more than imatinib in patients with a specific type of leukemia, due to better treatment tolerability and clinical response.

Contribution

The study demonstrates how clinical response and treatment tolerability impact HRQoL, supporting ponatinib's superiority over imatinib in Ph+ ALL.

Findings

Achieving clinical response was linked to significant improvements in HRQoL across multiple domains.

Treatment-related side effects significantly worsened HRQoL compared to no side effects.

Ponatinib showed better tolerability and longer response duration than imatinib, enhancing HRQoL.

Abstract

In the phase 3 PhALLCON trial (NCT03589326), ponatinib demonstrated superior efficacy, patient-reported treatment tolerability, and health-related quality of life (HRQoL) compared to imatinib in adults with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). To explore the association between clinical response and HRQoL and substantiate the superior effect of ponatinib over imatinib on HRQoL, we analyzed the impact of clinical response and treatment tolerability on changes in HRQoL.

HRQoL was assessed using the Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu) questionnaire and the EQ-5D-5 L. Treatment tolerability was assessed using the FACT-GP5 item “bothered by treatment side effects.” Linear mixed-effects regression models were used to examine changes in HRQoL over time, with clinical response status and patient-reported overall treatment tolerability as time-varying predictors, while controlling for significant covariates.

This analysis included data from 238 patients (159 ponatinib, 79 imatinib). Achieving clinical response (complete remission or incomplete remission) was associated with significantly better changes from baseline across all FACT-Leu domains and the EQ-visual analogue scale than not achieving clinical response (p < 0.05). Treatment-related side effects led to significantly and meaningfully worse changes in HRQoL than “not bothered by treatment,” with higher levels of “bother” associated with greater worsening in HRQoL from baseline.

Taken together with the better treatment tolerability and longer response duration of ponatinib compared to imatinib, these findings further substantiate the HRQoL benefit of ponatinib over imatinib in patients with Ph + ALL.

The online version contains supplementary material available at 10.1007/s00277-025-06635-0.