Positron emission tomography (PET) imaging of metabolic tumor burden at diagnosis and after induction therapy can help identify patients most at risk of follicular lymphoma (FL) recurrence, but more work is needed to differentiate high-risk and moderate-risk patients, suggested findings from a pooled analysis of data from three prospective clinical trials, published in Blood.
“Both total metabolic tumor volume (TMTV), computed on baseline PET, and end-of-induction PET (EOI PET) are imaging biomarkers showing promise for early risk stratification in patients with high tumor-burden follicular lymphoma,” reported lead author Anne Ségolène Cottereau, MD, from Cochin Hospital, René Descartes University, Paris, France, and colleagues. “This model enhances the prognostic value of PET staging and response assessment, identifying a subset of patients with a very high risk of progression and early treatment failure at 2 years.”
FL is the most frequently diagnosed indolent non-Hodgkin lymphoma. Immunochemotherapy and rituximab maintenance have improved patient outcomes in recent years, but 20% of patients will see disease progression within 2 years of their initial treatment, according to the data.
Only half of the patients experiencing early disease progression will survive for 5 years, the authors noted.
Risk-stratification tools are needed to identify which patients face the highest risk of recurrence, but the existing Follicular Lymphoma International Prognostic Index (FLIPI) and FLIPI2 prognostic calculators do not reliably identify these patients.
In order to more reliably identify high-risk patients as early as possible, the researchers used data from 159 patients with FL who had participated in three prospective trials, to build a prognostic model based on TMTV and EOI PET.
At a median follow-up of 65 months, both variables independently, negatively predicted disease progression, progression-free survival (PFS) and overall survival (OS). (For high TMTV [> 510 cm3], PFS hazard ratio [HR] was 2.34; 95% CI, 1.4–3.9; P = .001. For positive EOI PET, the PFS HR was also 2.34; 95% CI, 1.3–4.4; P = .0035. Overall survival HRs for high TMTV and EOI PET were 2.8 and 3.3, respectively [P = .08 and P = .036, respectively.])
In combination, high TMTV and positive EOI PET within 3 months of the completion of treatment successfully stratified patients into three risk categories: low risk (64%; low TMTV and negative EOI PET); intermediate risk (27.6%, either EOI PET-positive with small TMTV or high TMV and EOI PET–negative); and high risk (8%; patients with both high TMTV and positive EOI PET).
Two-year PFS was 90% in the low-risk group compared with 61% in the intermediate-risk group (HR, 4.8; 95% CI, 2.2–10.4; P < .0001. Two-year PFS was 46% in the high-risk group (high- vs low-risk: HR, 8.1; 95% CI, 3.1–21.3; P < .0001).
However, no statistically significant difference was seen in 2-year PFS between patients in the intermediate- and high-risk groups.
Five-year OS for low- and high-risk groups was 96% and 83%, respectively (P = .0016), and the proportion of deaths was 3% vs 31%, respectively (P = .003).
“Importantly, this model clearly identified the majority low-risk population, lacking either risk factor, with a median PFS not reached after more than 5 years of follow-up,” the researchers noted. “This population may likely benefit from the additional PFS advantage derived from rituximab maintenance, which was given to very few patients in this study.”
Once validated, the model might be applied “in comparison or in combination with” other biologically based prognostic tools, or with minimal residual disease assessment after treatment, they proposed.
“Such composite models will likely provide a platform for both risk- and response-adapted therapy for FL in the future,” with high-risk patients considered for referral to clinical trials, the investigators concluded.