The Adverse Consequences of Initial Watchful Waiting for Patients With Follicular Lymphoma

BACKGROUND: Patients with low tumor burden follicular lymphoma (FL) are commonly managed with watchful waiting (WW). The incidence of organ dysfunction and/or transformation at disease progression, and subsequent impact on outcomes is poorly understood. PATIENTS AND METHODS: Patients managed with WW during 1994 to 2011 were identified through the Alberta Lymphoma Database. Individuals receiving immediate rituximab (R)-chemotherapy were identified as a comparator group to those on WW who received R-chemotherapy at progression. Endpoints included transformation, organ dysfunction, time to progression, time to next treatment, progression-free survival (PFS) after chemotherapy, and overall survival (OS). RESULTS: We identified 238 patients managed with WW (28.9% of registry patients) during this 17-year period. The median follow up was 8.2 years. At a median of 29.9 months, 58 (24.4%) of these patients developed organ dysfunction and/or transformation. Of 169 (71%) patients who required therapy, 10-year OS was inferior for those with transformation (hazard ratio, 2.88; P = .002) and organ dysfunction (hazard ratio, 2.10; P = .028). PFS after R-chemotherapy and OS in patients without organ dysfunction and/or transformation was not affected by the initial WW period, compared with immediate R-chemotherapy. WW resulted in increased high risk FL International Prognostic Index scores at initiation of R-chemotherapy (45% vs. 20%), and more frequent transformation at progression (5-year risk, 17.8% vs. 3.5%; P < .001). Baseline characteristics did not predict organ dysfunction. CONCLUSION: Patients with FL accepting initial WW should be aware of the 1 in 4 risk of organ dysfunction and/or transformation, and subsequent inferior OS. Physicians should consider surveillance for progression to consider early therapy.