Blood cancers most commonly affect adults aged 65 years and older, with especially high rates among those aged 75 and above. Recent data from the World Health Organization indicate that most new cases of myeloid and lymphoid malignancies occur in these age groups. These prevalence rates are expected to grow as the global population of older adults continues to increase. For example, the incidence of multiple myeloma is projected to increase by 77% among those older than 65 by the year 2030, compared to 57% among those in younger age groups.1
Along with elevated prevalence rates, studies have demonstrated higher mortality rates in older adults compared with younger adults with hematologic malignancies. The highest mortality rates have been noted in patients aged 75 and older, and 1 study showed that individuals in this age group comprised more than 50% of deaths resulting from acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, and myeloma.1
Despite such figures, however, older adults are vastly underrepresented in clinical trials investigating treatments for hematologic malignancies. The authors of an earlier study found that only 25% of enrolled participants in the Southwest Oncology Group trials were aged 65 and older, although this age group represented 63% of cancer diagnoses. Underrepresentation was observed for 15 types of cancer except lymphoma, with especially low representation among patients with breast cancer — only 9% of participants were aged 65 and older though they represented 49% of breast cancer patients.2
In a review published online in February 2020 in Blood Reviews, Bindu Kanapuru, MD, and colleagues at the Center for Drug Evaluation and Research at the US Food and Drug Administration (FDA) in Silver Spring, Maryland, explored various aspects of this issue, including potential solutions.1
“[Dr Kanapuru and colleagues] outline a critical need amongst older adults with hematologic malignancies; advances in outcomes, morbidity, and mortality, cannot be improved unless older adults are enrolled in clinical trials,” said Ashley E. Rosko, MD, director of the Blood Cancer and Aging Program at The Ohio State University Comprehensive Cancer Center in Columbus. “The authors depict restrictive eligibility criteria both apparent — such as age limitations — and occult that preclude enrollment for this vulnerable population,” she explained to Hematology Advisor.
Working groups convened by the FDA Office of Hematology and Oncology Products and other stakeholders recently discussed potential ways to broaden eligibility criteria to include a larger number of older adults in clinical trials investigating hematological malignancies. Their recommendations include allowing enrollment of certain patients with creatinine clearance values 30 or less and those with mild or moderate hepatic dysfunction or cardiovascular dysfunction.1
“Additionally, dose modification guidance for patients that permit safe administration of these drugs in these patients should also be considered.”1 The authors suggest that while exclusion may be appropriate for patients with an ejection fraction of less than 35% for safety reasons, individuals should not be excluded based solely on ejection fraction, and some patients with prior or concurrent malignancies should be considered for inclusion if currently stable or treated successfully at least 2 years ago.
“The authors also address physician-related and patient-related barriers to clinical trial enrollment; and noted that patient refusal was the reason for non-enrollment in only 5% of cases,” Dr Rosko added. “This indicates that we as physicians are missing the mark, either in clinical trial design, communication, perceived benefits of standard therapies, or other aspects.”