Progression of disease may be effective endpoint for poor survival in lymphoma subtype

ATLANTA — Progression of disease within 24 months of diagnosis among patients treated with chemoimmunotherapy appears to be an effective early clinical endpoint of poor survival in follicular lymphoma and should be utilized to identify patients for prospective clinical trials, according to findings presented at the ASH Annual Meeting and Exposition.

Follicular lymphoma is the most common indolent lymphoma with a median survival of close to 20 years, according to study background. However, there is clinical heterogeneity with a subset of patients experiencing transformation, early recurrence or refractory disease.

Carla Casulo, MD, assistant professor of medicine at University of Rochester Medical Center, and colleagues conducted a pooled analysis of 13 randomized clinical trials of patients in both the pre- and post-rituximab era (n = 5,453).

Using the Follicular Lymphoma Analysis of Surrogacy Hypothesis data, the researchers aimed to evaluate the association between the Follicular Lymphoma International Prognostic Index (FLIPI) and other baseline factors on PFS within 24 months of trial enrollment. Additionally, the researchers aimed to validate the use of progression of disease within 24 months of diagnosis among patients treated with chemoimmunotherapy (POD24) as an early clinical endpoint in follicular lymphoma.

The researchers used a logistic regression model to evaluate the association between FLIPI, gender, and performance status with PFS within 24 months of trial enrollment.

Cox regression model with POD24 as a time-dependent covariate was used to evaluate the association between POD24 and OS. Additionally, the researchers conducted an analysis to evaluate the association of POD24 on OS for a subset of patients who were alive 24 months after trial registration.

Baseline beta2-microglobulin (B2M) data were available for nine of the 13 studies (n = 4,361).

Twenty-nine percent of patients progressed and 2.5% died without progressive disease within 24 months from trial registration.

Patients alive without progression at 24 months tended to be younger and more commonly had favorable performance status, limited stage, low FLIPI risk score, normal baseline hemoglobin and normal baseline B2M.

Being male (OR = 1.35; 95% CI, 1.19-1.52), having a performance status 2 (OR = 1.85; 95% CI, 1.47-2.38), and a FLIPI score of 3-5 (OR = 2.94; 95% CI, 2.38-3.57) appeared associated with an increased risk for progression or death before 24 months, according to a multivariable logistic regression model.

Results of the time-dependent Cox model, gender-adjusted and stratified by performance status and FLIPI, indicated an association between POD24 and poor subsequent OS (HR = 5.24; 95% CI, 4.63-5.93). Additional results of another analysis confirmed the association between POD24 and OS among patients alive 24 months after trial registration.

“We identified male gender, poor [performance status], high FLIPI score, and elevated baseline B2M as predictors of early death and progression,” Casulo said during the presentation. “These provide well-defined clinical factors for building comprehensive prognostic models in the future that incorporate clinical and molecular predictors of POD24. [These] results confirm POD24 as an early clinical endpoint of poor survival in follicular lymphoma that should be utilized to identify patients for prospective clinical trials.”

Reference:

Casulo C, et al. Abstract 412. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosures: Casulo reports research funding from Celgene; honoraria and travel support from Gilead; and a consultant role with Infinity.