Effectiveness of comprehensive geriatric assessment (CGA) in older patients with diffuse large B-cell lymphoma (DLBCL) and the impact of frailty in treatment tolerability and survival in a prospective, multicenter study.

Abstract

Abstract Introduction: In high-income countries, half of new hematological malignancy diagnoses are made in patients aged 75 years or older, of which lymphomas are the most common. Non-Hodgkin's lymphoma (NHL) mainly affects the older population, with a median age at diagnosis of 67 years. Older patients with Lymphoma are characterized by decreased physiological reserve, leading to reduced treatment tolerance, and complicating the diagnostic and therapeutic decision-making process. Although chronological age itself is not an accurate marker of an individual patient's biological situation and should not be used as a discriminatory variable when deciding on a therapeutic option, older patients with lymphoma often present age-related characteristics that influence prognosis and must be considered when choosing the most appropriate treatment. Therapeutic decisions must be based, not only on the tumor's characteristics, but also on the patient's physical, mental, and social ability to tolerate treatment, underlining the importance of multidimensional, multidisciplinary assessment. Methods: We conducted a prospective, multicenter study enrolling patients with Diffuse Large B-cell Lymphoma (DLBCL) older than 70 years referred to the Geriatric Hematology Clinic at two tertiary hospitals in Madrid (Spain) between May 2016 and March 2021. The comprehensive geriatric assessment (CGA) included comorbidity, polypharmacy, nutritional, functional, and mental status, geriatric syndromes, and life expectancy. CGA enabled patient classification into four groups (Type I or fit; type II or prefrail; type III frail; type IV or unfit) based on frailty assessment instrument scoring and clinical, functional, and mental status. Variables were compared using parametric and non-parametric statistical tests and Kaplan-Meier survival curves. Results: One hundred and twelve patients (55.4% women) were included. Median age (DE) was 79.9 (5.54) years. ECOG PS was 0 in 25 (22.5%), 1 in 56 (50.5%), 2 in 21 (18.9%), 3 in 9 (8.1%). Median CIRS score (DE) was 6.48 (4.14). After CGA, patients were classified as type 1 in 33 (29.5%), type 2 in 44 (39.3%), type 3 in 34 (30.4%), and type 4 in 1 (0.9%). In the univariate analyses, age, G8, CIRS-G, Lawton, ECOG, Barthel, FAC, Frail, SPPB and Geriatric síndromes were different among the 4 groups (p<0.05). Frail patients had more chance to discontinue therapy due to toxicity (20.6% vs 0.0%, p<0.001). Poor pronostic factor for Overall Survival (OS) were age (HR 1.07 (1.01-1.13), p=0.017), need of hospitalization (HR 1.22 ((1.03, 1.44), p=0.02), EPI score (HR 1.42 (1.16, 1.73), p=0.001), treatment discontinuation (HR 3.26 (1.26, 8.40), p=0.015), CGA profile (HR 2.52 (1.41, 4.48), p=0.002) and fragilization at the end of therapy (HR 9.46 (4.90, 18.3), p<0.001). Conclusion: Performance of standardized and systematic CGA permits older patients with lymphoma to be classified according to frailty, with significant differences in terms of clinical outcomes across groups. We propose incorporating CGA performed as part of the multidisciplinary care team to optimize therapeutic strategy for these patients.