The prognostic significance of PFS24 in follicular lymphoma following firstline immunotherapy: A combined analysis of 3 CALGB trials

Abstract

Follicular lymphoma (FL) patients treated with firstline R‐CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)‐based nonchemotherapy doublet trials: R‐galiximab (Anti‐CD80, CALGB 50402), R‐epratuzumab (Anti‐CD22, CALGB 50701), and R‐lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry. Twenty‐eight percent (48/174) of patients had early POD. After adjusting for the Follicular Lymphoma International Prognostic Index (FLIPI), patients with early POD from study entry had a worse OS compared with patients who did not progress within 2 years (HR = 4.33 (95% CI 1.50‐12.5), P = 0.007). For early POD, the 2‐year survival was 80% vs 99% for nonearly POD, and the 5‐year survival was 74% vs 90%, respectively. These findings suggest that the adverse survival of patients with early POD may be independent of initial treatment modality.

Positron-emission tomography–based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma

“…These observations suggested utilisation of a new clinical end-point to evaluate new treatment strategies, possibly leading to rapid approval by regulatory agencies. Furthermore, these observations suggested more intensive treatment approaches, including salvage chemoimmunotherapy followed by consolidative autologous stem cell transplantation, may be needed to improve the treatment outcome [3,5,6].…”

The simplified follicular lymphoma PRIMA‐prognostic index is useful in patients with first‐line chemo‐free rituximab‐based therapy

“…[5][6][7][8] Regardless of regimen, around 20-30% of patients will progress within 24 months from start of first-line therapy, often resulting in a short OS. [9][10][11][12] Therefore, risk stratification is essential, especially before initiation of therapy. The FL International Prognostic Index (FLIPI) is based on five bio-clinical parameters and is well-established for predicting OS.…”

“…Also chemo‐free rituximab‐containing therapy mostly leads to a long‐term OS 5–8 . Regardless of regimen, around 20–30% of patients will progress within 24 months from start of first‐line therapy, often resulting in a short OS 9–12 . Therefore, risk stratification is essential, especially before initiation of therapy.…”

The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival

“…POD24 has now been show to accurately predict overall survival in the context of chemotherapy alone, immuno‐chemotherapy and several ‘chemo free’ regimens (Lockmer et al ., 2018; Lansigan et al ., 2019; Moccia et al ., 2019). Bearing in mind that intra‐tumour heterogeneity and a complex tumour micro‐environment are considered critical to clinical outcome (Okosun et al ., 2014; Scott & Gascoyne, 2014), it seems likely that the specific sub‐groups POD24 patients may vary dependent upon treatment received.…”