Outcomes of Elderly Patients with DLBCL and Utility of Geriatric Assessment Tools to Predict Chemotoxicity

Background:

Treatment strategies in elderly DLBCL is challenging due to associated comorbidities. Conventional performance status indices do not account for physiologic effects of aging and may have limited predictive value. Geriatric assessment (GA) tools may help tailor treatment approaches but limited literature and lack of a baseline comparative cohort limits assessment of these tools. We aimed to perform a retrospective analysis on a large population of geriatric DLBCL patients to identify baseline outcomes patterns and prognostic factors. We also aimed to prospectively assess utility of GA tools for this patient population.

Patients and Methods:

We performed retrospective analysis of 619 newly diagnosed DLBCL patients >65 years between 2010 – 2022 treated at 2 cancer centers in Singapore. Logistic and Cox proportional-hazard regression models were used to evaluate parameters associated with progression free (PFS) and overall survival (OS). Survival curves were estimated using Kaplan-Meier method.

From 2022, prospective analysis of GA tools have been performed in our newly diagnosed DLBCL patients, including comprehensive geriatric assessment (CGA), ECOG and Cancer and Aging Research Group Chemotherapy Toxicity Tool (CARG-TT) scores. Relationship between the scoring systems and OS as well as incidence of severe TRAEs (Grades 3-5) was evaluated. Herein we report pilot data from the first 66 patients enrolled.

Results:

In the retrospective cohort, median age was 73 years (range 65-93), 62% of patients had advanced disease and 60% had high-intermediate/high risk IPI. 83% of patients received anthracycline (AC)- based while 10% received non-AC-based chemoimmunotherapy, and the rest were treated with palliation only. Patients who received AC-based chemoimmunotherapy had a median PFS of 100 months versus 12 months for those receiving non-AC-based therapy. With a median follow up of 42 months, the 5-yr PFS and OS was 56% and 62% respectively for the entire cohort. On multivariate analysis, older age and high ECOG scores (2-4) were predictive for poorer OS and PFS in this geriatric cohort. Majority of patients (88%) had an ECOG Fit status (ECOG PS 0-1).

In our prospective pilot cohort, 66 patients with median age of 74 (range 65-94) were analyzed. 85% of patients received an anthracycline based therapy while 7% were treated with palliative therapy only. CGA identified 26% patients as Fit, 62% as Pre-Frail, and 12% as Frail, while ECOG identified 85% (N=56) as Fit. Importantly, of ECOG-Fit patients, CGA identified 63% as Pre-frail and 7% as Frail. CGA also correlated better to chemotherapy risk calculated by CARG-TT compared to ECOG. Amongst ECOG-Fit patients, CARG-TT risk was intermediate in 14 patients (25%) and high in 13 patients (23%). In contrast, only 1 patient (6%) who was deemed fit by CGA had a high chemotoxicity risk per CARG-TT. 360 severe TRAEs were reported, with severe hematological TRAEs being more common (64% of events). Despite an upfront chemotherapy dose reduction strategy employed in more CGA Frail and Pre-Frail patients (75% and 73% respectively) compared to 29% of Fit patients, there was a trend towards a higher number of severe TRAES and hematological TRAEs in the Pre-frail (6.0 / 3.8 events) and Frail subgroup (6.1 / 3.3 events) compared to Fit patients (4.0 / 2.9 events) although this did not reach statistical significance (p>0.05) within the limits of this small cohort. A similar trend was noted with CARG-TT score, with higher TRAEs and hematological TRAEs (7.3 / 4.5 events) in the high risk CARG subgroups compared to the low risk subgroup (4.2 / 3.0 events). With a median follow up of 13 months, the median OS of Frail patients was 9 months while the median OS of Pre-Frail and Fit patients were not reached. Hazard ratios (HR) for death of Frail and Pre-Frail patients compared to Fit patients were 11 (95% CI 1.22-98.6), and 2.54 (95% CI 0.31-21.1) respectively.

Conclusion
In elderly patients with DLBCL, AC-based chemotherapy is associated with improved PFS and OS. Amongst ECOG-Fit geriatric patients, our pilot study suggests that CGA and CARG-TT may potentially improve prediction of chemotoxicity, while CGA better identifies patients at risk of poorer survival. GA tools should be integrated into patient screening at diagnosis to guide treatment modifications.