Phan V; Hershenson J; Caldarera L; Larkin SK; Wheeler K; Cortez AL; Dulman R; Briere N; Lewis A; Kuypers FA;
Yang E;
Pediatric blood & cancer [Pediatr Blood Cancer] 2023 May 29, pp. e30423.
Date of Electronic Publication: 2023 May 29.
Background: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.
Methods: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO 2 ), anaerobic threshold, O 2 pulse, VE/VCO 2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO 2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.
Results: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P 50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO 2 . The change in % predicted peak VO 2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.
Conclusion: In a pilot study of 10 youths with SCA, voxelotor treatment did not improve peak VO 2 in 9 out of 10 patients.