Frailty was significantly associated with overall survival (OS), event-free survival (EFS), frequency of higher grade adverse effects (AEs), and likelihood of proceeding to transplant in patients with lymphoma; however, the poor prognosis for patients with lymphoma may supersede the impact of frailty. These findings were reported in a poster presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
A secondary analysis was conducted using data from the phase 3 LY.12 clinical trial in an attempt to better understand the impact of frailty in clinical trials and how to counsel frail patients on their potential outcomes. All the patients had relapsed aggressive non-Hodgkin lymphoma and were randomly assigned to gemcitabine-dexamethasone-cisplatin or dexamethasone-high dose cytarabine-cisplatin chemotherapy prior to autologous stem cell transplant (ASCT).
Constructing a lymphoma clinical trials-specific frailty index (FI) using previously described methods was the primary objective. The researchers also examined the association of frailty (binary variable) with OS, EFS, hospitalization, AEs, serious AEs, and proceeding to transplant. This analysis included 619 patients, with 93 (15%) classified as frail, using a binary cut-off for frailty (<0.2).
The researchers found that frailty was strongly associated with OS (hazard ratio [HR], 2.012; 95% CI, 1.57-2.58), EFS (HR, 1.94; 95% CI, 1.53-2.46), frequency of the worst overall grade 3 or higher AE (odds ratio [OR], 2.65 [15% vs 6%]; P =.003) and likelihood of preceeding to ASCT (OR, 0.26; 95% CI, 0.15-0.43). However, it was not associated with hospitalization (OR, 1.52; 95% CI 0.97-2.40) or serious AEs (6% vs 4%; P =.3).
This current subanalysis of LY.12 data was used to develop a broadly applicable lymphoma clinical trials-specific frailty index. Frailty was significantly associated with OS, EFS, frequency of grade 3 or higher AE, and likelihood of proceeding to transplant. However, after controlling for lymphoma-related prognostic variables, frailty no longer has as significant an impact on outcomes. Revised international prognostic index (rIPI) score and Eastern Cooperative Oncology Group (ECOG) performance status were better predictors of OS and/or EFS.
The researchers concluded the impact of poor prognostic features of lymphoma superseded the impact of frailty alone in this younger clinical trial population (mean age, 53 years), and further testing is warranted in an external data set and an older population.
Vijenthira A, Li X, Crump M, et al. Development and testing of a lymphoma clinical trials specific frailty index: a secondary analysis of the LY.12 clinical trial. Presented at ASH 2021; December 11-14, 2021. Abstract 4076.