Refractoriness to immunochemotherapy in follicular lymphoma: Predictive factors and outcome.
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.
Department of Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerce Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Marc
http://orcid.org/0000-0002-0587-591X
M
Sorigue
Department of Hematology. ICO-Duran y Reynals, Hospitalet de Llobregat, Bacelona, Spain.
Santiago
S
Mercadal
Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.
Sara
S
Alonso
Department of Hematology, Hospital de Cabueñes, Gijón, Spain.
Ruben
R
Fernández-Álvarez
Department of Clinical Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Olga
O
García
Department of Clinical Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Miriam
M
Moreno
Department of Hematology. ICO-Duran y Reynals, Hospitalet de Llobregat, Bacelona, Spain.
Helena
H
Pomares
Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.
Miguel
M
Alcoceba
Department of Hematology, Hospital de Cabueñes, Gijón, Spain.
Esther
E
González-García
Department of Clinical Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Cristina
C
Motlló
Department of Hematology. ICO-Duran y Reynals, Hospitalet de Llobregat, Bacelona, Spain.
Eva
E
González-Barca
Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.
Alejandro
A
Martin
Department of Hematology. ICO-Duran y Reynals, Hospitalet de Llobregat, Bacelona, Spain.
Anna
A
Sureda
Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.
Dolores
D
Caballero
Department of Clinical Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Josep-María
JM
Ribera
Department of Clinical Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Juan-Manuel
JM
Sancho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
follicular lymphoma; immunochemotherapy; prognosis; refractoriness; survival; transformation