The authors noted that long-term hydroxyurea is the only disease-modifying drug for SCD, but it doesn’t work for all patients. Regular red blood cell transfusions provide an alternative. For patients in whom neither hydroxyurea nor regular blood transfusions are possible or effective, other interventions should be considered. Other approaches may include HSCT, gene therapy, or enrolling in a clinical trial.
Morgan McLemore, MD, medical director of the Georgia Comprehensive Sickle Cell Clinic at Grady Hospital in Atlanta and assistant professor of hematology and oncology at Emory University School of Medicine in Atlanta, Georgia, said there had been some concern that the average life expectancy in patients with SCD had either plateaued or declined. However, most adult clinics are now reporting an increased number of patients in their 40s, 50s, and beyond. “The article illustrates the challenges in caring for these individuals, because health issues that increase with age may be worsened by sickle cell or vice versa. As stated in the article, there are no clear guidelines for the treatment of older individuals. However, clearly patients may benefit from aggressive treatment of their disease,” Dr McLemore told Hematology Advisor.
Cancer Screening for Older Patients
Observational studies have demonstrated that progressive renal disease, worsening anemia, and incidental and overt neurological complications increase with age in patients with SCD. Morey A. Blinder, MD, of Washington University School of Medicine in St. Louis, Missouri, has been treating adult patients with SCD for more than 20 years. “There are a lot of opportunities for improvement,” Dr Blinder told Hematology Advisor. “Some of the patients end up with kidney failure or lung problems after age 40, so there would be opportunities to prevent some of those diseases.” He noted that after age 40, diabetes and hypertension become bigger issues in patients with SCD, and there is significant opportunity for prevention of these conditions through a variety of measures.
Dr Blinder and his colleagues conducted a study that included 397 adult patients with SCD (aged 18-76 years) who were seen between October 2011 and December 2015.2 Their research found that a hematologic malignancy occurred in 2.3% of patients over about 25 years. They concluded that patients with SCD should complete age-appropriate cancer screening for early detection. Dr Blinder said the findings highlighted the fact that routine medical care should not be ignored. “A number of malignancies were picked up incidentally. We should be screening for those,” said Dr Blinder. “It was a wakeup call to me.”
He said it is paramount for patients to have a primary care physician by middle age, but that can be difficult in a lot of settings. “To add in another layer of medical visits in some patients — it is not possible. We push for having a primary care doctor for all patients, but we find for some it is not workable,” explained Dr Blinder.
On the Horizon
The toolbox for managing SCD-related complications in this patient population is growing. Several therapeutic agents are in phase 2 and 3 trials. Crizanlizumab, a humanized antibody to P-selectin, is showing promise for preventing acute pain in patients with SCD. In a phase 2 trial, crizanlizumab was found to reduce SCD-related pain crises.3
A phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT01119833) is currently under way that is studying the efficacy and safety of a pan-selectin inhibitor called rivipansel (GMI-1070) for the treatment of vaso-occlusive events in hospitalized patients with SCD. Also in clinical development is a hemoglobin modifier called voxelotor, an oral, once-daily therapy for patients with SCD that has received breakthrough therapy designation by the US Food and Drug Administration.
1. Thein SL, Howard J. How I treat the older adult with sickle cell disease [published online September 11, 2018]. Blood. doi: 10.1182/blood-2018-03-818161
2. Thomas T, Thomas D, French K, Blinder MA. Malignancy in Patients with Sickle Cell Disease: A Single Center Observational Study. Blood. 2016;22:48-67.
3. Kutlar A, Kanter J, Liles DK, et al. Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis [published online October 8, 2018]. Am J Hematol. doi: 10.1002/ajh.25308