Older adults underrepresented in clinical trials for blood cancers

Issue: January 25, 2018

ATLANTA — Although adults aged 65 to 74 years appeared adequately represented in hematologic malignancy clinical trials between 2005 and 2015, those aged 75 years or older were disproportionately underrepresented, according to a retrospective analysis conducted by the FDA and presented at the ASH Annual Meeting and Exposition.

“The FDA has implemented regulations and issued guidance aimed at improving inclusion of older adults in pivotal clinical trials,” Bindu Kanapuru, MD, hematologist at Inova Fairfax Hospital and Virginia Hospital Center and a medical officer with the FDA, said during her presentation. “We collected demographic data from clinical trials of hematologic malignancies supporting FDA approvals over 10 years.”

Hematologic malignancies are frequently diagnosed among patients aged older than 65 years.

Further, from 2020 to 2030, cases of multiple myeloma that occur among older adults are expected to increase from 36% to 77%, leukemia from 33% to 69%, and non-Hodgkin lymphoma from 33% to 67%.

Kanapuru and colleagues retrospectively analyzed demographic datasets of patients enrolled to trials submitted to the FDA in support of the approval of new or supplemental indications for hematologic cancer therapies from 2005 to 2015. They compared rates of enrollment with SEER data on age distribution of incidence by cancer type.

Overall, reserachers identified 44,144 patients enrolled in 210 clinical trials evaluating hematologic malignancies — 45% (n = 19,908) in lymphoma trials; 24% (n = 10,465) in 33 chronic myeloid leukemia trials; 22% (n = 9,609) in 48 multiple myeloma trials; and 2% (n = 1,052) in acute myeloid leukemia or myelodysplastic syndrome trials. Another 6% of patients were enrolled in trials classified as “other.” Less than 1% (n = 403) were enrolled in acute lymphoblastic leukemia trials.

Overall, 61% of FDA trials for hematologic malignancies from 2005 to 2015 included patients aged younger than 65 years, whereas 39% included patients aged 65 years or older. Additionally, more than 85% of the participants in ALL trials were aged younger than 65 years.

Compared with the cancer population in the United States, clinical trials for lymphomas, CLL, CML and multiple myeloma enrolled a disproportionately higher percentage of patients aged younger than 65 years.

Enrollment in the 65 to 74 age group appeared slightly lower than SEER incidence for lymphoma (24.6% vs. 23.1%) and CML (16.5% vs. 20.7%) trials. Conversely, a higher percentage of patients in the 65 to 74 age group were enrolled in CLL (36.6 vs. 28.8%) and myeloma (34.6% vs. 29.2%) trials compared with SEER data.

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However, patients aged 75 years or older were consistently underrepresented in lymphoma, CLL, CML and myeloma trials compared with the SEER incidence cases in the same age groups.

The greatest difference occurred in CML trials, where 3.8% of patients enrolled were aged 75 years or older, compared with SEER incidence of 28.6%. Multiple myeloma (13.5% vs. 33.3%), lymphoma (9.2% vs. 29.2%) and CLL (16.5% vs. 38.3%) trials also were disproportionately underrepresented.

“This analysis shows how important it is for us to actually do more subgroup analysis for patients in this age group,” Kanapuru said. “I am heartened by the conclusion that patients in the 65 to 74 age group are represented adequately, but we have to understand the patients on clinical trials are the healthier patients and may not represent those 65- to 74-year-olds in the real world.

“I’m also at a loss to explain why there is such a disproportionate representation in patients with CML older than 75 years,” Kanapuru added. “This was particularly striking and the reasons for this discrepancy are not clear from this analysis.”

According to Gregory A. Abel, MD, MPH, associate professor of medicine at Harvard Medical School and director of the older adult hematologic malignancy program at Dana-Farber Cancer Institute, a strength of the study is its use of clinical trials submitted as evidence for FDA approvals.

“On the other hand, the comparisons made to the U.S.-based SEER registry are not necessarily the best because many of those trials are international, so not all of the subjects are American,” Abel, who was not involved with the study, told HemOnc Today in an interview. “They also looked at incidence of diseases, and not necessarily people who would meet clinical trial criteria outside of age. For example, many patients in these trials may have had relapsed disease. What we’re interested in knowing is what percentage of older patients get onto trials matched for eligibility criteria, not necessarily just matched for disease incidence.”

The study underscored the need for clinical trial criteria that includes patients aged older than 75 years, Abel said.

“No one wants to have older patients on clinical trials do poorly because they are frail,” he said. “There has to be a way of having older patients be eligible for trials but still screened to make sure they can tolerate an experimental drug. [Although] this study was a terrific effort by the FDA, this point wasn’t addressed, and there are very few trials that include rigorous criteria to assess robustness.” – by Chuck Gormley

Reference:

Kanapuru B, et al. Abstract 861. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosures: The authors and Abel report no relevant financial disclosures.