Gene therapy in sickle cell disease: Attitudes and informational needs of patients and caregivers

Abstract

Background: Sickle cell disease (SCD) is an inherited blood disorder that results in serious morbidity and early mortality. Novel therapies for SCD, most notably genetic therapies (GTs) and HLA-mismatched donor hematopoietic cell transplantation, are in clinical trials. While potentially curative, these interventions are some of the most intensive treatments for SCD and are associated with serious and life-altering side effects, which may manifest several years after treatment. Little is known about knowledge, beliefs, and attitudes of individuals with SCD, or their caregivers, toward existing and these emerging therapies.

Methods: Patients with SCD at least 13 years of age (n = 66) and caregivers (n = 38) were surveyed about knowledge, attitudes, and beliefs surrounding treatments for SCD.

Results: Only 4.8% felt "extremely knowledgeable" about GT for SCD while the majority (63.4%) reported little knowledge. Overall, health literacy was low among respondents. Most respondents had a neutral attitude regarding the safety of GT for SCD, and whether it was a good treatment for the disorder (56.7% and 58.6%, respectively). Only a few respondents endorsed the idea that GT was "unsafe" or "not a good treatment" (5.8% and 4.8%, respectively). There was an association between increasing knowledge about GT and agreement that it is safe (p = .012) and a good treatment for SCD (p = .031).

Conclusions: Given that very few patients with SCD feel knowledgeable about GT and a majority have neutral feelings about the safety and utility of this new approach, culturally appropriate patient-centered education is urgently needed as these treatments get regulatory approval and proceed to the clinic.

Trial registration: ClinicalTrials.gov NCT03745287 NCT04443907 NCT05456880.

Keywords: gene therapy; hematology/oncology; patient education.

Figure 1:. Self-Reported Knowledge About Gene Therapy, Bone Marrow Transplantation, and Hydroxyurea as Potential Treatments for Sickle Cell Disease

Using a five-point Likert Scale, participants were asked to report their knowledge of two potentially curative treatments for Sickle Cell Disease (SCD) alongside a commonly available disease-modifying therapy (Hydroxyurea). Self-reported knowledge about Hydroxyurea therapy for SCD was significantly greater than for either bone marrow transplantation or gene therapy (P < 0.0001, for both comparisons).

Figure 2:. Participant Assessment of Safety and Utility of Various Treatments for Sickle Cell Disease

Using a five-point Likert Scale, participants were asked to rate the safety and utility of two potentially curative treatments for Sickle Cell Disease (SCD) (Gene Therapy, Bone Marrow Treatment) alongside two commonly utilized disease-modifying interventions (Hydroxyurea and Chronic Blood Transfusion Therapy).

Figure 3:. Impact of Potential Treatment Risks and Benefits on Participant Willingness to Undergo Gene Therapy or Bone Marrow Transplant

Figure 3A depicts the likelihood of potential therapy-related side effects on one’s decision to undergo gene therapy (GT) or bone marrow transplant (BMT), while Figure 3B depicts the impact of potential treatment benefits on one’s decision to undergo GT or BMT. Significant p-values (P < 0.05) are included when applicable.

Figure 4:. Impact of Psychosocial Factors on Participant Willingness to Undergo Gene Therapy or Bone Marrow Transplant

The potential impact of external psycho-social factors influencing a respondent’s decision to undergo gene therapy (GT) or bone marrow transplant (BMT). Significant p-values (p < 0.05) are included when applicable.

Figure 5:. Association Between Participant Characteristics and Beliefs about Gene Therapy, Bone Marrow Transplantation, and Hydroxyurea as Treatment for Sickle Cell Disease Measured by Goodman and Kruskal’s Gamma coefficient (γ)

The figure displays the results of an association analysis (Goodman and Kruskal’s Gamma) looking at the relationship between participant characteristics and their beliefs about gene therapy (GT), bone marrow transplant (BMT), and Hydroxyurea (HU) as interventions for Sickle Cell Disease (SCD). Significant associations are indicated with one asterisk (*) for p < 0.05 and two asterisks (**) for p < 0.001. See results for full explanation of the significant associations.