How do Follicular Lymphoma patients do on a Watch and Wait approach? Molecular, pathological, and clinical features
- Other support (specified) Teaching activities Amgen, unrelated to this topic.
Follicular lymphoma (FL) is the most prevalent type of indolent non-Hodgkin lymphoma in Western countries, characterized by considerable heterogeneity in clinical trajectories and molecular features. The watch and wait (WW) approach involves monitoring patients without initiating treatment, often chosen for those diagnosed with asymptomatic, disseminated FL. In the Netherlands, approximately 40% of patients diagnosed between 1989 and 2016 were managed using this strategy. Although the prognosis is generally favorable, predicting the duration of a WW strategy is challenging. A prediction model including clinical and/or biological features at diagnosis would be valuable for personalizing follow-up care. This study aimed to evaluate survival and prognostic factors in a real-world cohort of FL patients managed with a WW strategy.
We retrospectively analyzed clinical, pathological, and molecular data from 124 patients who underwent WW management (WW-cohort) to assess their prognostic impact and compared these findings to a cohort of 91 patients receiving R-C(H)OP (Rituximab, Cyclophosphamide, (Doxorubicin), Vincristine, and Prednisone) at diagnosis (R-C(H)OP-cohort). Molecular analysis was performed using hybrid capture based next generation sequencing by the EuroClonality DNA capture assay, targeting 83 lymphoid related genes.
Patients selected for a WW approach demonstrated favorable outcome, with a median event-free survival (EFS) of 29 months (range 3-233 months). Notably, 36% of these patients never required systemic treatment despite a median follow-up of 192 months (range 3-244 months). Overall survival (OS) did not differ between the WW-cohort and R-C(H)OP-cohort (p=0.71). Within the WW-cohort hemoglobin levels <12.9 g/dL and elevated KI67 proliferation index were associated with inferior EFS (Hazard ratio (HR) 2.5 p=0.01, HR 1.033 p=<0.001 respectively), while the traditional FL international prognostic index (FLIPI) showed only a trend toward significance (HR 1.47, p=0.08).
Mutational profiles were heterogeneous in both cohorts. In the WW-cohort B2M mutations were associated with inferior EFS (HR 3.01, p=0.03), although mutations were found in only four patients. The m7-FLIPI score was associated with EFS in both cohorts (WW-cohort; HR 1.99 p=0.02, R-C(H)OP-cohort HR 1.93 p=0.049). Comparison of genetic profiles between these cohorts revealed no significant differences, even when comparing patients with disease progression within 24 months in the R-C(H)OP-cohort and those achieving EFS exceeding 5 years in the WW-cohort, representing extremes of the clinical spectrum with different OS (p=<0.001).
The WW approach proves to be a viable management strategy for FL, demonstrating favorable OS outcomes. However, predicting the duration of the WW period and providing patients with a meaningful perspective remains a challenge. The genetic information identified in this study did not sufficiently predict the clinical course, underscoring the need for further research to refine prognostic tools and improve individualized patient management.