Abstract

Background and objective Fludarabine in combination with cyclophosphamide (FC) plus rituximab (R) is an effective treatment for newly diagnosed as well as relapsed follicular lymphoma (Tam 2004; Keating 2005; Sacchi 2007). Maintenance treatment with R, after different induction treatments, improves overall and progression-free survival (Forstpointner 2006; van Oers 2006). Therefore, we aimed to evaluate the efficacy and safety of the FC-R regime followed by maintenance doses of R.

Patients and Methods We present an intermediate report of the one-arm study in which 75 previously untreated patients with a diagnosis of follicular non-Hodgkin’s lymphoma in Ann Arbor stage II–IV were included between October 2004–2006. Seventy four were assessed for safety after receiving at least one FC-R dose (F: 3x25 mg/m2 and C: 1 g/m2; R: 375mg/m2), and 72 for response to treatment. Patients aged 53.4 years in average, one in five showed bulky disease and 72.2% Ann Arbor IV staging. FLIPI index determined 23.9% patients with low (0–1) score, 38% with intermediate (2) and 38% with poor score (3). A total of 47 patients presented some molecular alteration in PB or BM.

Results Induction therapy was delivered throughout 4–6 courses, resulting in 91% complete responses (CR) and 9% partial responses (PR) (Table 1). From the patients who presented monoclonal population at diagnosis, 40 were evaluated for molecular response after induction and only 1 remained MDR positive for bcl2/IgH. Overall survival (OS) at 24 months was 87.5%, and two patients presented progressive disease within this period. The median OS has not been reached at this evaluation. To the date, 262 adverse effects grade 3–4 (32.6%) have been documented (80.9% neutropenias) and 80 infectious complications were recorded (23.8% grade 3–4). Three patients died from respiratory diseases, two from acute leukemia, and six from other causes.

Table 1

EVOLUTION OF RESPONSEEvaluated Response at End of Induction Therapy
Evaluated Response Post-Course 3Assesable End Ind. (n=67)Missing End Ind. (n=5)
CR: complete response; uCR: unconfirmed CR; PR: partial response; NE: not evaluated; WD: withdrawn; EX: exitus. 
Assesable PC3 (n=70) CRITERIA CR PR NE WD EX 
14 CR 12 
32 uCR 31 
24 PR 16 
Missing PC3 (NE) 
72 Total 61 
EVOLUTION OF RESPONSEEvaluated Response at End of Induction Therapy
Evaluated Response Post-Course 3Assesable End Ind. (n=67)Missing End Ind. (n=5)
CR: complete response; uCR: unconfirmed CR; PR: partial response; NE: not evaluated; WD: withdrawn; EX: exitus. 
Assesable PC3 (n=70) CRITERIA CR PR NE WD EX 
14 CR 12 
32 uCR 31 
24 PR 16 
Missing PC3 (NE) 
72 Total 61 

Conclusions The FC-R has proven a potent antitumoral activity in untreated follicular lymphoma patients, rendering very high clinical and molecular responses. However, as reported in similar studies (Hochster 2007 ASCO), the high incidence of prolonged neutropenias and lymphopenias developed as consequence of the chemotherapy regime, questions the safety of the induction treatment.

Author notes

Disclosure:Research Funding: Work supported by an unrestricted grant from Roche Farma SA. Off Label Use: Newly designed regime