Elderly Patients Significantly Underrepresented in Hematology Clinical Trials

Patients aged 75 years or older diagnosed with hematologic malignancies appear significantly underrepresented in clinical trials submitted to the U.S. Food and Drug Administration (FDA), according to a retrospective analysis.

The researchers noted that these results, presented at the ASH Annual Meeting and Exposition, are particularly concerning given that the number of adults aged 75 and older who are diagnosed with blood cancers is only expected to rise as the population ages. Currently, one out of five patients diagnosed with most blood cancers is age 75 and above, according to a press release on the study.

“For example, by 2030, 77 percent of new multiple myeloma cases will be in patients aged 65 years or older, compared with 57 percent in those younger than 65,” Bindu Kanapuru, M.D., medical officer for the FDA, said at the meeting, held Dec. 9-12, in Atlanta. “This trend is similar in leukemia and non-Hodgkin’s lymphoma.”

The researchers analyzed demographic datasets of more than 44,000 patients enrolled in clinical trials as part of the FDA approval process for hematologic cancer therapies from 2005 to 2015. Patients were grouped into disease categories based on the diagnosis specified for trial entry and age — younger than 65 years, 65 to 74 years, and 75 years or older. They were then compared with the age distribution of incidence cases by site using the SEER database.

In total, 45 percent (19,908) of patients were enrolled in lymphoma trials; 24 percent (10,465) in chronic myeloid leukemia (CML) trials; 22 percent (9,605) in multiple myeloma (MM) trials; 2 percent (1,052) in acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) trials; 6 percent (2,711) were classified as “other” trials, which included myeloproliferative neoplasms and trials enrolling multiple malignancies; and less than 1 percent (403) in acute lymphoblastic leukemia (ALL) trials.

More than half of patients were 65 years or older in these trials, excluding those enrolled in the CLL and AML/MDS trials. In particular, more than 85 percent of elderly patients comprised the ALL trials.

Patients under 65 years of age were overrepresented in all trials compared with the incidence of cancer in this age group. For example, researchers found that 79.7 percent of patients enrolled in trials for CML were under 65, but only 50.6 percent of patients diagnosed with CML are in this age group.

On the other hand, patients aged 75 and older account for 28.6 percent of CML diagnoses, yet this age group made up a mere 3.8 percent of those enrolled in clinical trials to evaluate new treatments for the disease. They were also consistently underrepresented in trials of new treatments for lymphoma, CLL, and multiple myeloma compared with the incidence of each of these cancers in that age group.

“Regardless, I am at a loss to explain why patients with CML, there is such a disproportion among patients aged 75 or older,” Kanapuru said.

On the plus side, both arms of elderly patients aged 65 to 74 years old mirrored one another in the proportion of patients enrolled in lymphoma and CML trials.

“This analysis shows how important it is for us to actually do more subgroup analyses of patients over 65 years,” Kanapuru said. “I am heartened by the conclusion that we have at least patients in the 65 to 74 year-old age group represented adequately. But we have to understand that the patients on clinical trials still are the healthier patients and may not represent the 65 to 74-year-old of-age patients in the real world.”

Reference:Kanapuru B, Singh H, Myers A, et al. Enrollment of Older Adults in Clinical Trials Evaluating Patients with Hematologic Malignancies — the Food and Drug Administration (FDA) Experience. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta. https://ash.confex.com/ash/2017/webprogram/Paper106804.html.