The past decade has led to advances in medicine that at one time seemed unimaginable for patients with life-threatening blood cancers and blood disorders. Patients who once had few treatment options available now have hope for a cure. However, these potentially life-saving treatment advances may be out of reach for some patients unless the healthcare ecosystem makes a concerted effort to end access and outcomes disparities.
For many patients with diseases like leukemia, lymphoma or sickle cell disease, hematopoietic cell transplantation (HCT) or another cellular therapy is the best treatment option. Yet not every patient who needs this treatment gets it. For those who do, outcomes are not always equal.
To end the disparities, we must understand and address recurring barriers to treatment.
HLA led to HCT disparities historically
Why are outcomes unequal? For decades, genetic differences based on ancestry—measured by a system called HLA or human leukocyte antigen—created a barrier. It was the major reason some patients were more likely to receive allogeneic HCT—also known a bone marrow transplant (BMT) or a blood stem cell transplant—than others. Allogeneic HCT uses blood stem cells from a related or unrelated donor.
When using traditional techniques for allogeneic transplant, physicians look for a match at specific HLA markers. There are 8 HLA genes that are most important. A so-called “perfect match” is an 8 out of 8 match. Historically, a mismatch led to worse outcomes for patients. With each mismatch, there was about a 10% decrement in five-year survival.
The problem lies in the fact that not everyone has a perfect match in their family or on worldwide unrelated donor registries. In the U.S., the majority of registry members are non-Hispanic White and the overall makeup does not yet match the current racial and ethnic diversity reflected in the latest U.S. census. HLA matches are more likely among people of the same ethnicity or race. That makes the likelihood of finding a fully matched unrelated donor significantly lower for patients who are racially or ethnically diverse.
For example, a patient who is Black or African American has about a 29% chance of finding a fully matched available unrelated donor. One who is White has a 79% chance.
In addition, the population has become—and will continue to get—more diverse. With more diversity in HLA genes, more people have uncommon HLA which makes it even harder to find a fully matched donor. That means continuing with the status quo of traditional HCT matching techniques is not an option.
Disparities have continued in the age of CAR-T
The treatment landscape for patients with blood cancers and disorders has also rapidly changed with the dawn of cell therapies like chimeric antigen receptor T-cell (CAR-T) therapies. Before 2017, no CAR-T therapy had received U.S. Food and Drug Administration (FDA) approval. Today, six CAR-T therapies are FDA-approved for blood cancers.
While these new therapies are a positive for patients, access and outcomes disparities exist. For example, a retrospective study using the Vizient clinical database found that:
- Less than 12% of patients who received CAR-T therapy were from low-income neighborhoods.
- Black and African American patients were two times less likely to receive CAR-T therapy.
- Patients who had Medicaid insurance or were uninsured were less likely to receive CAR-T therapy.
Another study by the Pediatric World CAR Consortium indicated the potential for outcomes and access disparities based on race. The group specifically focused on outcomes for Black and African American pediatric patients.
While there was low representation of Black and African American patients (5.5%)—a limitation of the study—when compared to pediatric patients of other races, Black and African American patients had lower rates of complete remission (57% vs. 86%) and overall survival at six months (43% vs. 86%) and one year (43% vs. 73%) after receiving CAR-T.
In addition, a higher percentage of Black and African American patients did not receive CAR-T therapy, received significantly more lines of therapy pre-CAR-T, and had HCT prior to CAR-T therapy more often. This could suggest they had delayed access to CAR-T treatment compared to other racial and ethnic groups.
Other common barriers have led to disparities, but solutions exist
To overcome access and outcomes disparities for both HCT and cell therapy, other common barriers must also be addressed. These include unequal representation in clinical trials, high treatment costs and insurance barriers, providers’ and patients’ lack of knowledge about treatment advances, and treatment center location and associated patient travel expenses.
While the barriers are daunting, there are solutions.
Ongoing research has already led to treatment advancements in HCT that lessen the HLA barrier by allowing for greater HLA mismatching with excellent outcomes. This opens the door for many more patients to receive the potentially life-saving treatment. Analyses of donor registries show that a donor is available for virtually all those in need of HCT when allowing for HLA match levels down to 5 of 8.
Historically, people who are ethnically diverse are underrepresented in clinical trials. To overcome the disparity, clinical trial sponsors can include specific diversity targets in accrual plans and monitor accrual throughout the trial. In fact, the FDA has released draft guidance with recommendations for clinical trial sponsors to develop a Race and Ethnicity Diversity Plan to include with new IND applications to improve enrollment of patients who are racially and ethnically diverse.
The population studied can also make a difference. For example, an HCT study focused on those without a matched unrelated donor—a population that is historically more ethnically diverse. In this study, 48% of patients enrolled were ethnically diverse, which is almost double the typical enrollment in HCT clinical trials.
High treatment costs and insurance barriers do not have easy solutions. HCT and cell therapy insurance coverage alone is complex. Covered services and payment models vary by plan and, for those with Medicaid coverage, by state.
This is an area where grassroots efforts can lead to change. For example, many states have introduced biomarker testing legislation that would require health insurance coverage for biomarker testing. HLA typing and testing is an example of a biomarker test that is used in HCT.
To help more patients access HCT and cell therapy, hematology/oncology practices and centers that provide HCT and cell therapy must work together. Partnerships between the practices and centers can improve knowledge gaps and lead to earlier patient referral for treatment. Hematology/oncology providers would also have the information they need to educate patients about all the treatment options available to them.
These partnerships can also help patients overcome travel barriers. Transplant centers and cell therapy centers are not in every community and many patients must travel long distances to access care. Extended hotel stays are often necessary in the weeks before and after treatment. The out-of-pocket costs—which are in addition to treatment-related costs—can cause extreme financial hardship.
A “shared care” model between the hematology/oncology practice and transplant or cell therapy center could help some patients stay closer to home for some parts of their care pre- and post-treatment.
Ending access and outcomes disparities in HCT and cell therapy will require a collaborative effort, from clinicians, associations and non-profit organizations in the hematology/oncology, HCT and cell therapy communities to policy makers and payers. All patients must have equal access to life-saving treatments, and have the same opportunity to thrive after treatment. It won’t be easy, but it is necessary. The status quo is not an option.
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