Geriatric risk model for older patients with diffuse large B-cell lymphoma (GERIAD): a prospective multicenter cohort study

Korean J Intern Med. 2024 May;39(3):501-512. doi: 10.3904/kjim.2023.265. Epub 2024 Jan 30.

Abstract

Background/aims: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS).

Results: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%.

Conclusion: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

Keywords: Diffuse large B-cell lymphoma; Dose intensity; Prognosis; Simplified geriatric assessment; Toxicity.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Comorbidity
  • Decision Support Techniques
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Frail Elderly
  • Frailty / diagnosis
  • Frailty / epidemiology
  • Geriatric Assessment*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / mortality
  • Male
  • Predictive Value of Tests
  • Progression-Free Survival
  • Prospective Studies
  • Republic of Korea / epidemiology
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Doxorubicin