Improving Survival for Adults With Sickle Cell Disease

— Gene therapy, better supportive care offer promise of decades of good-quality life

Life expectancy for patients with sickle cell disease (SCD) has more than tripled in the past 50 years. Life expectancy in the 1970s for a person with SCD was less than 20 years, with some estimates as low as 14 yearsopens in a new tab or window. By 2022, half of all patients living with SCD were 60 or older at deathopens in a new tab or window, a decade longer than in 2008.

"I had a visitor in my clinic, whose parents are from Kenya, and we saw a patient who was 72, and he couldn't believe it," Sana Saif ur Rehman, MD, of Washington University in St. Louis, told MedPage Today. "He couldn't believe that we can support people to live that long but also with good quality of life."

Several key developments have contributed to improved survival and other outcomes in adults with SCD. Noting that she has cared for patients with SCD for about a decade, Saif quickly pointed to the approval of two gene therapiesopens in a new tab or window as key factors in survival gains.

"We can now offer an option for cure, for longevity, for long life with good quality of life, to people who did not have good matches for bone marrow transplant," she said. "We have yet to see how gene therapy will pan out over the long term. We don't have any survival data yet, but it just makes sense. If at the end of gene therapy you come out with normal hemoglobin, not a lot of hemolysis or sickling, it would add years to your life and organ protection and disease modification. I think it is very exciting."

Still, she remains realistic about gene therapy's potential impact on the totality of disease burden.

"But gene therapy also is very intensive and resource heavy, and I don't think many centers can offer it," said Saif. "Even if you are at a center that can offer this option, you may not be a candidate for various reasons. So, while it will be life changing for a subset of our patients, I don't think it's something that will change every patient's life."

The numbers provide additional context for the potential impact of gene therapy on SCD. In 2025opens in a new tab or window -- 2 years after the therapies' approval -- about 165 patients received the two treatments combined, including patients with beta-thalassemia, an approved indication for exagamglogene autotemcel (exa-cel, Casgevy) since 2024. About 100,000 people in the U.S. have SCD.

Cost remains a substantial societal issue, as exa-cel had an introductory list priceopens in a new tab or window of $2.2 million and lovotibeglogene autotemcel (lovo-cell, Lyfgenia) an introductory price of $3.1 million. Medicaid covers the therapies in the states that participateopens in a new tab or window in the CMS Cell and Gene Therapy Access Model. Patients with private insurance might pay as much as $40,000 in out-of-pocket costs.

Beyond gene therapy, specialists in SCD have learned how to provide better care.

"We provide more wraparound care, more multidisciplinary services, at least in comprehensive care centers," said Saif. "We are more proactive about screening for organ damage, getting our patients connected to the resources they need."

In an effort to make SCD clinical care more broadly available, some comprehensive care centers periodically host conferences for community-based hematologists and other clinicians. The translation is difficult, particularly in rural or resource-limited settings.

"I do think there is a difference in the care a patient receives at a center of excellence versus clinical practices," said Saif. "It's such a rare and complex disease and requires a certain level of expertise to manage it."

Evidence-based data for optimal SCD care remain limited. In an effort to fill the information void, the National Alliance of Sickle Cell Centers periodically publishes consensus recommendations regarding care for patients with SCD, most recently consensus standardsopens in a new tab or window for transitioning young patients with SCD into adult care.

"There are so many questions, such as how to care for a patient who is pregnant," said Saif. "How should we manage pain most appropriately? What about mental health needs?"

Every patient should have a comprehensive annual visit that includes a careful review of the patient experience since the last visit. One of the most common is pain management.

"Pain is a hallmark of this disease," said Saif. "A detailed discussion of pain control is very important."

In general, pain management shifted use of opioids from a primary role to an adjunctive role. A thorough discussion of pain management should include use of nonsteroidal pain relievers and behavioral therapy. Patients should be screened for sleep apnea and nocturnal hypoxemia, which can be major sources of pain if untreated, said Saif. Every patient should have a detailed review of emergency department visits and hospitalizations, which frequently involve pain episodes.

With longer survival, treating the disease process has become a point of emphasis. As an example, Saif points to the patient with the SS genotype, which is associated with the worst survival.

"We used to say, 'Your hemoglobin is 7, which is half of what a normal person should have, but you're not having a lot of pain, and you're doing pretty well because your body is just used to running on an empty tank,"' she said. "I don't have that conversation anymore. Now I say, 'I am looking at 10, 20, 30 years of life for you, and I won't be able to get you there unless I treat your sickle cell disease.'

"I am more proactive about offering hydroxyurea or transfusion therapy or options for cure. In the old days, I think we were less concerned about anemia if other things were fine. Now I focus more on treating the sickle cell disease. We can't just put a patient on opioids and leave it at that."

Blood pressure, iron levels, vitamin D levels, and urine protein are important aspects of good care. Questioning patients for signs of pulmonary hypertension and right-sided heart failure can lead to early recognition of common complications that might have been overlooked in the past.

"The goal is to recognize end-organ damage before it happens," said Saif. "This is how we get patients to their 60s and 70s."

Despite significant progress, substantial unmet needs still exist. Given the large number of patients who do not receive gene therapy or transplants, lack of disease-modifying therapies remains a huge void in SCD care. After hydroxyurea, which can make a substantial impact on life, drugs with disease-modifying potential have not panned out for the most part, said Saif.

Addressing patients' psychosocial burden is also high on the list of unmet needs. Mental health issues, such as anxiety, depression, and post-traumatic stress disorder, are just one component of the burden, said Saif. Many patients face ongoing challenges related to transportation, child care, time off from work (for those who are employed). The burden is compounded by lack of mental health resources in many communities for patients with SCD.

Looking ahead, Saif sees promise in some of the investigational therapies in various stages of development. In particular, she is hopeful for drugs designed to increase expression of fetal hemoglobin.

"One of the gene therapies also increases expression of fetal hemoglobin, but that also requires chemotherapy and manipulation of stem cells and returning the stem cells to the patient," said Saif. "There are certain compounds in early-phase studies that are in the form of an infusion or pill that help your body make more fetal hemoglobin, and those are things that a majority of our patients might have access to."