SIRPa¹ macrophages are increased in patients with FL who progress or relapse after frontline lenalidomide and rituximab

Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R²). Moreover, mechanisms of resistance to R² in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R². A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein a [SIRPa]), and CD274 (also known as programmed cell death-ligand 1 [PDL1]), was used to stain tissue biopsy specimens collected before initiation of R² and at the time of progression. Among 156 patients with advanced-stage FL treated with frontline R², 33 (21%) relapsed or progressed and required second-line therapy, after a median of 33 months (range, 1-122 months). Second-line therapy was chemoimmunotherapy in 16 (48%) patients and other therapy in 17 (52%). The overall response rate was 78%, and complete response rate was 72%. Median progression-free survival was significantly longer in patients who received chemoimmunotherapy compared with other therapy (99 vs 25 months; P 5 .004). Three macrophage populations were significantly increased in tissue samples collected at progression compared with before frontline treatment: CD68¹CD115¹ (P 5 .02), CD68¹CD115¹CD172a¹ (P 5 .02), and CD68¹CD163¹CD172a¹ (P 5 .01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R².