LAUSR

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first‐line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first‐line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first‐line response assessment were considered ICT refractory. Three hundred forty‐three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high‐risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2‐microglobulin were correlated with refractoriness, and refractoriness, high‐risk FLIPI score, and β2‐microglobulin were correlated with overall survival (OS). Compared with ICT‐sensitive, ICT‐refractory patients had a higher incidence of histological transformation (5‐year cumulative incidence 25% [14%‐39%] vs. 6% [3%‐10%], P < .001), a higher rate of refractoriness to second‐line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5‐year OS probability 38% [95% CI 23%‐53%] vs. 87% [82%‐92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high‐FLIPI scores, B symptoms, and elevated serum β2‐micrglobulin. Immunochemotherapy‐refractory patients had a worse prognosis than ICT‐sensitive patients, and current treatment options for this subgroup are not satisfactory.