Older Patients Underrepresented in Trials of Hematologic Malignancy Treatments

People over the age of 65 represent the majority of those diagnosed with hematologic malignancies, but they account for only about one-third of patients enrolled in clinical trials designed to assess new anti-cancer therapies, according to Bindu Kanapuru, MD, and colleagues at the U.S. Food and Drug Administration (FDA).

“Until now, there has been little information about the enrollment of adults with hematologic cancers,” Dr. Kanapuru said during her presentation at the 2017 ASH Annual Meeting. “Based on our findings, the occurrence of cancer is much higher in adults over 75 years, compared with the proportion of patients in this age group who enroll in clinical trials.”

To examine age-related disparities in clinical trial enrollment, investigators conducted a retrospective analysis of trials submitted to the FDA in support of approval of new or supplemental indications for blood-cancer treatments between 2005 and 2015. The pool comprised 44,144 patients.

Patients were grouped by age (<65, 65-74, and ≥75 years) and disease type. Enrollment rates were then compared with data on the rate of occurrence of each cancer by age group from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute between 2010 and 2014.

Participants were included in trials of treatments for:

  • lymphoma, including chronic lymphocytic leukemia (CLL): 45% (n=19,908)
  • chronic myeloid leukemia (CML): 24% (n=10,465)
  • multiple myeloma (MM): 22% (n=9,605)
  • acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS): 2% (n=1,052)
  • acute lymphocytic leukemia (ALL): <1% (n=403)
  • other hematologic malignancies: 6% (n=2,711)

Except for trials investigating treatments for CLL and AML/MDS, more than 50 percent of participants were <65 years (see TABLE 2).

“We weren’t surprised to see that, overall, adults aged 75 years and older were underrepresented in clinical trials, as this is common across cancer trials,” Dr. Kanapuru said, “but we were surprised by the magnitude of the gap for this age group, particularly for CML trials.”

Nearly 80 percent of patients enrolled in trials for CML were younger than 65 years, while only 50 percent of patients diagnosed with CML from SEER data fell in that age group. Similarly, in the ALL trials, more than 85 percent of participants were younger than 65 years (see TABLE 3).

The disparity grew larger among older patients: Those 75 years or older accounted for 29 percent of patients with CML, but only 4 percent of trial participants.

Dr. Kanapuru also highlighted some encouraging insights from this analysis. Among patients aged 65 to 74 years, the proportion enrolled in lymphoma (excluding CLL) and CML trials essentially mirrored the reported incidence of blood cancers in this age group. In MM and CLL trials, the proportion enrolled in the 65-74 age group was higher than the reported incidence in this group. However, adults older than 75 years were still underrepresented in FDA clinical trials, despite the high number of diagnoses of incident hematologic cancers in this age group.

She noted that there are multiple barriers to enrolling older adults in clinical trials. For example, trial exclusion criteria often prohibit people with a history of previous cancers or comorbid or coexisting illnesses, which older adults are more likely to have, compared with younger individuals.

“Doctors may hesitate to enroll these older patients because they aren’t sure how they will tolerate investigational medications,” Dr. Kanapuru said, also citing the heterogeneity of the older population as a reason for their underrepresentation. “You can have one 75-year-old who is healthy and another person of the same age who is frail and has a lot of coexisting illnesses,” she said.

Study limitations include its retrospective design and variance in the data collected in the SEER database.

The authors report no financial conflicts.


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. Abstract #861. Presented at the 2017 American Society of Hematology Annual Meeting, December 11, 2017; Atlanta, GA.