Clinical research has immense value, leading to the discovery of new treatment pathways and improved patient outcomes. However, such gains may have less positive impact on patients who are ineligible for clinical trials, because the data do not represent how the clinical outcomes affect unincluded populations.
Mark A Fiala, BS, CCRP, Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, explored this issue as it applies to patients with multiple myeloma in his presentation on Saturday, December 3, at the 58th American Society of Hematology Annual Meeting and Exposition in San Diego, CA.
“Over the past two decades....a glut of new knowledge about the biology, genetic profile, and prognostic factors of the disease have become available,” Fiala said. “However, much of this research has excluded patients with low performance status and those with impaired renal function or marrow reserve; therefore, relatively little is known about these patients who are largely ineligible for clinical trials.”
Fiala and colleagues collected data from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway, looking at research that corresponded with interim analysis from the CoMMpass study; CoMMpass amasses relevant clinical information and sequential tissue samples. They then initiated a secondary data analysis of the MMRF CoMMpass study to compare the disease manifestation, treatment, and prognosis of ineligible patients to the overall MM population.
Study authors defined ineligibility for clinical trials as one or more of the following at time of MM diagnosis.
- Eastern Cooperative Oncology Group performance status 3 or 4
- Creatinine ≥ 2.0 mg/dL or receiving dialysis
- Absolute neutrophil count (ANC) < 1.0x109/L or receiving growth factor support
- Platelet count < 50,000 x109/L or receiving platelet transfusion support
They then compared the demographics, baseline presentation (International Staging System [ISS] stage, marrow and extramedullary disease burden, and chromosomal abnormalities), and first-line treatment of 799 ineligible patients. Studied patients had a median age of 64 years, and most were male (61%) and Caucasian (76%). Subsequently, researchers initiated a multivariate Cox regression analysis to examine event-free survival (EFS) defined as the interval from diagnosis to disease progression or death.
Study authors found that participants who were ineligible for clinical trials were similar to eligible patients in terms of demographics and stem cell transplant (SCT) use, but they also showed several key differences. Ineligible patients were more likely to
- Have higher-risk disease, defined by the International Staging System (ISS)
- Have deletion of 17p
- Be less likely to receive immunomodulatory drugs during first-line therapy.
“After controlling for ISS stage, deletion of 17p, first-line treatment, and SCT utilization, patients ineligible for clinical trials had a 56% increase in risk of disease progression or death,” said Fiala.
“Newly diagnosed MM patients with low performance status, impaired renal function, or marrow reserve have long been considered a high-risk group and, thus, most clinical trials have excluded them” he said. “IMIDs are contraindicated for these patients due to its myelotoxicity which further limits treatment options. After adjusting for differences in treatment, these patients still have poorer outcomes.”