For example, at the June 5 plenary session of the American Society of Clinical Oncology, Paul Richardson, MD, presented results of the DETERMINATION trial. More than 40,000 attendees heard his message that, in patients with newly diagnosed multiple myeloma (MM), up-front high-dose melphalan with autologous hematopoietic stem cell transplant (HSCT) support is associated with a significantly longer median progression-free survival of 67 months, compared with 46 months for patients randomized to delayed transplantation. The 5-year overall survival is similar for both arms.
While I and many of my colleagues in the field of transplantation used this data to strongly encourage MM patients to undergo HSCT as consolidation of their initial remission, others – including many investigators on the DETERMINATION trial – reached a starkly different conclusion. They suggested that delaying transplant was a valid option, since no survival benefit was observed.
Bias, when defined as a prejudice in favor of or against a specific treatment on the part of physicians and patients, has not been carefully studied in the realm of cellular therapies. However, physician and patient perceptions or misperceptions about the value or toxicity of a specific therapy are probably major drivers of whether a patient is referred for and accepts a particular form of treatment. In my specialization, that would mean either a stem cell transplant or other forms of cell therapy.
As with other medical procedures, in my field there are significant disparities in the use of transplantation among patients of different racial, ethnic, and age groups. Rates of both auto- and allo-HSCT are significantly higher for Whites than for African Americans. Hispanic patients have the lowest rates of utilization of auto-HSCT. Patients over the age of 60 have an eightfold risk of nonreferral to an HSCT center. Obviously, these nonreferrals reduce access to HSCT for older patients, particularly if they are seen at nonacademic centers.
One must question whether these disparities are caused by the physicians not believing in the value of transplantation, or simply not understanding its value? Or do they just lack the time to refer patients to a transplant center?
Socioeconomic factors, insurance status, age, and psychosocial characteristics all impact access to HSCT, yet some older patients with fewer economic resources and less insurance coverage still undergo the procedure. Is that because their physicians spent time educating these patients about the potential value of this treatment? Is it because the physicians went the extra mile to get these patients access to HSCT?
Physician preference also plays a significant role in whether a patient receives an allo-HSCT for acute myeloid leukemia and myelodysplastic syndrome. In a large survey of hematologists and oncologists performed by Pidala and colleagues, half of those surveyed agreed with the statement: “I feel the risk (morbidity and mortality) after HSCT is very high.” Most indicated that they “feel outcomes of unrelated donor HCT are much worse than matched sibling HCT.”
More importantly, more than one-third of those surveyed agreed that, “because of the high risks of allogeneic HSCT, I refer only after failure of conventional chemotherapy.” They voiced this opinion despite the fact that mortality rates after HSCT have been reduced significantly. With modern techniques, outcomes of unrelated donors are as good as with sibling donor transplants, and national guidelines strongly recommend that patients get referred before they become refractory to chemotherapy.
What can we do about this problem? Obviously, physician and provider education is important, but primary care physicians and general oncologists are already bombarded daily with new information. Relatively rare conditions like those we treat simply may not get their attention.
Personally, I think one of the most effective ways to overcome bias among physicians would be to target patients through a direct advertising campaign and public service announcements. Only by getting the attention of patients can they be directed to current, accurate information.
This solution could reduce the impact of physician biases or misperceptions and provide patients with greater access to lifesaving cell therapies.
Dr. Giralt is deputy division head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center in New York.