Researchers identify higher risk of early chemotherapy-related death in older patients with DLBCL

Although diffuse large B-cell lymphoma (DLBCL) is a curable disease in most patients aged 65 years or older, these patients are also at higher risk of chemotherapy-related death within the first 30 days of treatment.

To quantify the risk of early fatality and identify risk factors, researchers led by Adam J. Olszewski, MD, Brown University and Rhode Island Hospital, looked at Medicare claims linked to Surveillance, Epidemiology and End Results registry (SEER-Medicare) data for more than 5,500 patients, ages 65 and older, with DLBCL who were treated with contemporary immunochemotherapy—rituximab, cyclophosphamide, and vincristine in combination with doxorubicin, mitoxantrone, or etoposide. Their findings are published online in the September issue of JNCCN - Journal of the National Comprehensive Cancer Network. Complimentary access to the study is available until November 30, 2016.

"Identifying the risk of severe complications is challenging given the paucity of data and heterogeneity in physiologic reserve among patients of the same age," said Dr. Olszewski.

Dr. Olszewski and his fellow researchers identified six key risk factors for early death in older patients with DLBCL: disease-related symptoms ("B-symptoms"), chronic kidney disease, poor performance status, prior use of walking aids or wheelchairs, prior hospitalization within the past 12 months, and upper endoscopy within the past 12 months. They also found the risk of early death within the first round of treatment was significantly higher in patients 75 years or older. Of patients studied, those with zero to one identified risk factor have very low risk of early death, while those who presented with four or more were 13 times more likely to die from chemotherapy complications.

Furthermore, researchers noted that administration of prophylactic granulocyte-colony stimulating factor (G-CSF) was associated with lower probability of early death in the high-risk group.

"It is equally important to realize that a majority of older patients without risk factors can safely receive curative immunochemotherapy. Enhanced supportive care and monitoring should be provided for high-risk groups," said Dr. Olszewski. "The first month of treatment, when patients are compromised both by active lymphoma and toxicities of chemotherapy, is a period of particular concern, as nearly one in four patients were hospitalized during that time. While comprehensive geriatric assessment remains the gold standard for risk assessment, our study suggests that readily available data from electronic medical records can help identify the high-risk factors in practice."

While further research is warranted, immediate opportunity for lowered rates of chemotherapy-related mortality while treating patients most likely to tolerate the treatment lay in the identification of the six risk factors for early death that can be culled from electronic heath record data and integrated into digital support tools for enhanced decision-making at point of care, the researchers noted. Furthermore, the study indicated an opportunity for preventive intervention with prophylactic G-CSF.

"It is important to identify patients at risk for treatment-related complications particularly for the selection of patients that may benefit from 'pre-phase' therapy to mitigate risk. The model proposed by Olszewki, et al. provides a simple assessment of treatment-related risk," said Andrew D. Zelenetz, MD, PhD, Memorial Sloan Kettering Cancer Center, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel Chair for Non-Hodgkin's Lymphomas.