Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study

Authors

Vivian Phan, Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Jared Hershenson, Division of Cardiology, Children's National Hospital, Washington, District of Columbia, USA.
Laura Caldarera, Child Cardiology Associates, Rockville, Maryland, USA.
Sandra K. Larkin, Department of Pediatrics, University of California San Francisco, Oakland, California, USA.
Kari Wheeler, Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Ana Lucia Cortez, Inova Fairfax Children's Hospital, Falls Church, Virginia, USA.
Robin Dulman, Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Noravy Briere, Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Angela Lewis, Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Frans A. Kuypers, Department of Pediatrics, University of California San Francisco, Oakland, California, USA.
Elizabeth Yang, Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.

Document Type

Journal Article

Publication Date

5-29-2023

Journal

Pediatric blood & cancer

DOI

10.1002/pbc.30423

Keywords

cardiopulmonary test; exercise; oxygen dissociation curve; peak VO2; sickle cell; voxelotor

Abstract

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 ), anaerobic threshold, O pulse, VE/VCO slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO . 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 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO . The change in % predicted peak VO 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 plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO in 9 out of 10 patients.

APA Citation

Phan, Vivian; Hershenson, Jared; Caldarera, Laura; Larkin, Sandra K.; Wheeler, Kari; Cortez, Ana Lucia; Dulman, Robin; Briere, Noravy; Lewis, Angela; Kuypers, Frans A.; and Yang, Elizabeth, "Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study" (2023). GW Authored Works. Paper 2846.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2846

Department

Pediatrics