SIRPα+ Macrophages Are Increased in Patients With FL Who Progress or Relapse After Frontline Lenalidomide and Rituximab

Authors

Mario L Marques-Piubelli
Edwin R Parra
Lei Feng
Luisa Solis Soto
Mariana Gallardo
Sushanth Gouni
Felipe Samaniego
Mansoor Noorani
Fredrick B Hagemeister
Jason R Westin
Hun Ju Lee
Maria A Rodriguez
Sattva S Neelapu
Jillian R Gunther
Nathan H Fowler
Christopher R Flowers
Ignacio I Wistuba
Loretta J Nastoupil
Francisco Vega
Paolo Strati

Publication Date

6-14-2022

Journal

Blood Advances

Abstract

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 α [SIRPα]), 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 = .004). Three macrophage populations were significantly increased in tissue samples collected at progression compared with before frontline treatment: CD68+CD115+ (P = .02), CD68+CD115+CD172a+ (P = .02), and CD68+CD163+CD172a+ (P = .01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. Therapies targeting specific macrophage populations may yield novel approaches for improving outcomes with frontline R2.

Keywords

Humans, Lenalidomide, Lymphoma, Follicular, Macrophages, Neoplasm Recurrence, Local, Retrospective Studies, Rituximab

DOI

10.1182/bloodadvances.2022007104

PMID

35359004

PMCID

PMC9198921

PubMedCentral® Posted Date

6-2-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes