Hydroxyurea

Patient education, lifestyle modifications, and medication review are crucial for managing priapism in sickle cell disease (SCD). Alpha-adrenergic agonists like etilefrine and phosphodiesterase type 5 inhibitors (PDE5i) are used to treat SCD-related priapism. Hormonal manipulation with cyproterone acetate, 5-α reductase inhibitors, ketoconazole, and diethylstilbestrol shows limited efficacy. Hydroxyurea, red cell exchange therapy, crizanlizumab, voxelotor, and L-glutamine offer potential benefits but lack specific trials for priapism. Allogeneic hematopoietic stem cell transplantation and gene therapy are curative options with ongoing research.

From Jan 2021 to Aug 2022, 105 PMF patients were randomized across 38 centers; 71 to gecacitinib 100 mg BID, 34 to HU 500 mg BID. Gecacitinib showed higher 24-week SVR35 (64.8%) vs HU (26.5%), rapid spleen response at 12 weeks, and better TSS50 at week 24. Gecacitinib improved anemia and platelet levels, with fewer serious AEs and lower cytopenia rates. Median follow-up was 17.5 months for gecacitinib and 15.9 for HU. 85 patients entered the extension phase, with 17 crossing over from HU to gecacitinib.

Allogeneic stem cell transplantation (allo-SCT) showed improvements over standard of care (SOC) in silent cerebral infarct (SCI) incidence, social quality of life (QoL), working memory, and processing speed for patients with sickle cell anemia (SCA) over 10 years of follow-up, according to the DREPAGREFFE-2 clinical trial.

Navtemadlin monotherapy improved biomarkers of disease burden in relapsed/refractory myelofibrosis patients, including reductions in CD34 cells, driver mutation burden, serum inflammatory cytokine levels, and correlated with SVR, suggesting anti-clonal activity and disease modification.

A Phase II trial in Ghana found hydroxyurea beneficial for HbSC sickle cell disease, improving red blood cell volume, fetal hemoglobin levels, and reducing crises and hospitalizations. The study, presented at ASH 2024, aims to dispel the myth of HbSC as a milder form, advocating for its treatment with hydroxyurea.

Despite the U.S. approval of gene therapies Casgevy and Lyfgenia for sickle cell disease, their use has been minimal due to complex treatment processes and limited accredited centers. Both therapies offer near-curative benefits but require extensive preparation and carry significant risks. Despite initial slow uptake, developers Vertex and Bluebird anticipate growth as more centers become accredited. The high cost and potential risks remain significant considerations for patients.

Navtemadlin (KRT-232), an MDM2 inhibitor, reduced biomarkers of disease severity in R/R myelofibrosis patients, suggesting it targets disease-driving cells and alters progression. In the phase 3 BOREAS trial, navtemadlin showed significant reductions in CD34+ cells, driver gene VAF, and pro-inflammatory cytokines, correlating with spleen volume response and improved bone marrow fibrosis.

Etavopivat reduced annualized vaso-occlusive crises rate vs. placebo in sickle cell disease, increased hemoglobin levels, reduced fatigue, and improved hemolysis markers, according to HIBISCUS trial data presented at ASH Annual Meeting and Exposition.

Hydroxyurea showed fewer painful vaso-occlusive events and hospitalizations in hemoglobin SC patients, though higher dose-limiting toxicities were observed.

Hydroxyurea showed manageable safety and reduced painful vaso-occlusive events and hospitalizations in HbSC disease, though phase 2 trial did not meet primary endpoint of dose-limiting toxicities. A phase 3 trial is needed to confirm clinical benefits.