Changing the scene on sickle cell disease

Overview of Presentations with access to videos on demand (EHA subscription needed) 


Presentation ID p432-1


Presenter: Clark Brown, Atlanta, United States

The study authors conclude that Voxelotor increased Hb and decreased markers of hemolysis in pediatric patients with SCD aged 4 to 11 years, the majority of whom were receiving stable hydroxyurea. The drug was well tolerated, without new adverse safety signals. According to the study authors, these results were consistent with those in adults and adolescent patients aged ≥12 years treated with voxelotor 1500 mg once daily in the HOPE trial. The authors further conclude that these results support the use of voxelotor in pediatric patients with SCD ≥4 years of age as a potential strategy for early mitigation of the morbidity and mortality associated with SCD.


The study authors conclude that LentiGlobin treatment resulted in complete resolution of severe VOEs up to 24 months post-treatment and decreased patient-reported pain intensity from baseline. There was near pancellular HbAT87Q expression and improved SCD pathophysiology after therapy. The safety profile of LentiGlobin treatment regimen remains generally consistent with myeloablative single-agent busulfan conditioning and underlying SCD.


The study authors present the largest study reporting on results from concurrent systematic cognitive screening and MRI/A surveillance in adults with SCD, with all major phenotypes represented. They confirm with this data the high prevalence of neurologic lesions in a contemporary cohort. They show that the presence of IWML on screening MRI/A is associated with neurocognitive deficits. Independent radiological assessment is underway to grade the severity of the radiological lesions and correlate these findings with dementia. Multivariable analyses are presented at the meeting and highlight an area of unmet need in the management of neurocognitive morbidity in SCD.


The study authors conclude that results from the Phase 2a and OLE studies (as of data cut-off) demonstrate that daily dosing of up to 200 mg IMR-687 was safe and well-tolerated as a monotherapy or in combination with HU. Treatment with 200 mg IMR-687 was shown to increase F-cells (%) with trends for improved HbF, markers of hemolysis and rate of VOCs. A Phase 2b study testing IMR-687 at higher doses was initiated to further explore IMR-687 as a disease-modifying therapy for SCD.


The study authors conclude that these data further indicate that VCAM1 haplotypes we previously associated with pediatric cerebral vasculopathy and hemolysis in SCA, induce higher VCAM1 expression potentially affecting both cerebral and systemic vasculopathy risk. The differential endothelial expression of VCAM1, NOS3, and HMOX1 after proinflammatory and/or pro-oxidative stimuli also reinforces their genetic modulation role in SCA systemic vasculopathy.