According to data being presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, fragility in patients with diffuse large B-cell lymphoma (DLBCL) is significantly associated with 1-year mortality.

“Previous studies have demonstrated that frailty is associated with mortality among patients with non-Hodgkin lymphoma including [DLBCL]. However, no studies have examined frailty in an unselected population-based sample of patients with DLBCL, nor have data on health care utilization been considered as a potential mediator of this relationship,” wrote Abi Vijenthira, MD, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, and colleagues.

Thus, using population-based healthcare data, Dr Vijenthira et al conducted a retrospective cohort study to determine whether or not frailty is tied to 1-year survival in patients with DLBCL, and if its impact is mediated by healthcare utilization during receipt of chemotherapy.

A total of 5527 patients (median age, 75 years) receiving first-line chemo-immunotherapy for de novo DLBCL (n = 5216) or transformed follicular lymphoma (n = 311) between January 2006 and December 2017 were included in the study.

“Frailty was defined by modifying a previously validated score developed for use with population-based data in Ontario, comprising 30 multidimensional variables,” the investigators explained.

“Patients were categorized as ‘frail’ (score >0.21) vs. ‘non-frail’ (score ≤0.21). Covariates included age, number of comorbidities based on the Johns Hopkins Aggregated Diagnosis Groups (ADGs), and health care utilization during chemotherapy,” they continued.

The primary outcome measure was the link between frailty and 1-year mortality according to Cox regression, and secondary outcomes included healthcare utilization, chemo-immunotherapy exposure, and cause of death.

Ultimately, 2699 (49%) patients were deemed frail. These patients tended to be older (median age, 76 vs 74 years), and the difference in mortality between patients who were frail and non-frail was most prominent in the initial year after treatment began.

Within 90 days of receiving first-line rituximab, 14% (n = 370) of frail patients had died compared with 7% (n = 185) of non-frail patients (P <.0001), and within 1 year of receiving first-line therapy, 32% (n = 868) of frail patients had died compared with 20% (n = 553) of non-frail patients (unadjusted hazard ratio [HR], 1.8; 95% CI, 1.6-2.0; P <.0001). Of the frail patients who died within 1 year (n = 868), approximately 35% had only received 1 chemotherapy cycle.

When multivariable modelling controlling was used for age, number of ADG comorbidities, and healthcare utilization during chemotherapy, frailty was independently tied to 1-year mortality (adjusted HR, 1.6; 95% CI, 1.5-1.8; P <.0001).

When measured in quartiles, the relationship between survival and frailty remained consistent (HR, 1.6; 95% CI, 1.3-1.9 for Q2; HR, 2.0; 95% CI, 1.7-2.4 for Q3; HR, 2.7; 95% CI, 2.3-3.2 for Q4; P <.0001).

Of note, patients who were frail were significantly more likely to receive only 1 chemotherapy cycle than non-frail patients (14% vs 7%, respectively; P <.0001); they also had higher rates of healthcare utilization during chemotherapy (mean emergency department visits, 0.75 + 1.47 vs 0.59 + 1.17, respectively; P <.001; mean hospitalizations 0.9 + 1.12 vs 0.72 + 1.05, P <.001).

Frail patients were also more likely to die from DLBCL than their non-frail counterparts (38.3 vs 29%, respectively; P <.0001).

“Frailty is significantly associated with one-year mortality in patients with newly diagnosed DLBCL, even after adjusting for age, comorbidities, and health care utilization,” Dr Vijenthira and colleagues wrote.

“Frailty appears to be associated with poor tolerability of chemotherapy and a higher likelihood for requiring acute hospital-based care, and future analyses will explore whether this is related to patients suffering increased treatment-related toxicity,” they concluded.—Hina M. Porcelli

Vijenthira A, Mozessohn L, Nagamuthu C, et al. Frailty Is Associated with Increased One-Year Mortality in Patients with Newly Diagnosed Diffuse Large-B-Cell Lymphoma: A Population-Based Study. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 742.