Early Relapse in First-Line Follicular Lymphoma: A Review of the Clinical Implications and Available Mitigation and Management Strategies

Abstract

Chemoimmunotherapywith rituximab (R-chemo) or obinutuzumab (G-chemo) is standard of care for patients with previously untreated symptomatic or high-tumor-burden follicular lymphoma. Median progression-free survival (PFS) with R-chemo plus R maintenance exceeds 10 years, and G-chemo plus G maintenance improves PFS relative to the corresponding R-containing regimen. Despite these positive results, a sizable proportion of patients continue to progress during or shortly after initial treatment. While no single definition of early relapse has been established, progression of disease within 24 months of initial treatment (POD24) is now widely accepted as a critical adverse prognostic factor. Multiple studies have shown increased mortality risk in patients with POD24 versus those without POD24. Unfortunately, tools for the assessment of POD24 risk are suboptimal, and it is not currently possible in clinical practice to identify individual patients who are at increased risk for early relapse. Treatment strategies for patients with POD24 are not well defined. G-chemo regimens appear to reduce the risk of POD24 relative to R-chemo regimens, although the impact on survival outcomes remains unclear. Beyond standard therapy, autologous stem cell transplant and emerging treatment modalities, such as bispecific antibodies and chimeric antigen receptor T-cells, may have a role in future management. Until standard treatments are defined, mitigating the risk of early relapse with effective up-front treatment remains the priority.

A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes

“…In rare instances, spontaneous remission may occur and is thought to require the generation of an antitumor response following immunologic stimuli, e.g., viral infection or injury (Potts et al, 2017). Lastly, patients who experience p rogression o f d isease within 24 months of initial treatment (POD24), termed early relapsers, are the subset with the shortest overall survival and should be considered the highest risk (Casulo et al, 2015; Casulo et al, 2021; Freeman et al, 2019; Maurer et al, 2016; Rodgers et al, 2021). Despite the urgent clinical need, a predictive tool and consensus treatment approach for early relapsers does not exist (Rodgers et al, 2021).…”

“…Lastly, patients who experience p rogression o f d isease within 24 months of initial treatment (POD24), termed early relapsers, are the subset with the shortest overall survival and should be considered the highest risk (Casulo et al, 2015; Casulo et al, 2021; Freeman et al, 2019; Maurer et al, 2016; Rodgers et al, 2021). Despite the urgent clinical need, a predictive tool and consensus treatment approach for early relapsers does not exist (Rodgers et al, 2021). Therefore, a greater understanding of the cell-intrinsic and -extrinsic factors governing progression and therapeutic outcomes is needed for risk-adapted management of FL patients.…”

Ascites as First Atypical and Only Clinical Manifestation of De Novo Follicular Lymphoma

“…Follicular lymphoma (FL) is the most common indolent non-Hodgkin’s lymphoma (NHL) in the Western world and is usually initially detected in lymph nodes [ 1 ]. Extranodal occurrence most often happens as a result of disseminated nodal disease but the extranodal site can also be primarily localized.…”

Early progression in follicular lymphoma in the absence of histological transformation or high‐risk Follicular Lymphoma International Prognostic Index still has a favourable outcome

“…Moreover, this group of poor prognosis is heterogeneous and even after adjusting for the Follicular Lymphoma International Prognostic Index (FLIPI) score, early relapse confers an increased risk of death by itself. The FLIPI score has a sensitivity and specificity to predict POD24 of 60%–78% and 56%–62% respectively 20,23 . Thus, some patients with a high FLIPI at diagnosis will not become POD24 and behave well and, conversely, some POD24 cases show notable survival after the first relapse/progression (SF1R).…”

“…The FLIPI score has a sensitivity and specificity to predict POD24 of 60%-78% and 56%-62% respectively. 20,23 Thus, some patients with a high FLIPI at diagnosis will not become POD24 and behave well and, conversely, some POD24 cases show notable survival after the first relapse/progression (SF1R). In this setting, most published studies concerning relapsed or refractory follicular lymphoma (RRFL) have been designed to identify adverse prognostic factors detected at the time of diagnosis and also analyse outcomes at lymphoma diagnosis.…”