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Primary prophylaxis with pegfilgrastim reduces chemotherapy disruptions due to febrile neutropenia in patients with indolent Non-Hodgkin Lymphoma after bendamustine-rituximab induction

Mar 29, 2017

This month, in Supportive Cancer Care, Claudio Cerchionefrom the Azienda Ospedaliera Universitaria Federico II, Naples, Italy, and colleagues published results of their prospective study, which compared secondary prophylaxis with filgrastim (control) versusprimary prophylaxis with pegfilgrastim (peg group) in patients with iNHL after induction with bendamustine-rituximab.

In total, 122 patients with untreated iNHL were eligible for analysis with a median age of 45.3 years (range, 31–77). The histological subtypes were FL (n=83), MZL (n=32), SLL (n=4), and LPL (n=3).

Key Highlights:


  • Induction: bendamustine IV 90mg/m 2given over 30–60 min on days 1 and 2 of each cycle) plus rituximab 375mg/m 2on day 1 of each cycle; every 4 weeks for up to 6 cycles
  • G-CSF prophylaxis strategy:
    • First period (March 2013 to August 2014): 61 pts received secondary prophylaxis with filgrastim SC 5μl/kg/day for at least 3 days, on demand if ANC <1,000/mm 3
    • Second period (since July 2014): 61 pts received primary prophylaxis with pegfilgrastim SC 6mg on day 4 from first course of immune-chemotherapy in each cycle


  • In the control group, in the 366 cycle of BR performed, median number of vials of filgrastim administered = 3 (range, 0–5); started in mean from the second course (range, 1–3)
  • Mean of nadir in ANC:
    • Control group = 1,220/mm 3(range, 300–1,700) for a mean duration of 9 days (range, 7–11)
    • Peg group = 1,734/mm 3(range, 880–2,110) for a mean duration of 5 days (range, 3–9)
  • Pts who disrupted chemotherapy schedules due to febrile neutropenia:
    • Control group = 7/61 (11.5%); 3 were time-disruptions and 4 were dose-disruptions
    • Peg group = 1/61 (1.6%; time disruption)
    • Peg significantly associated with fewer incidences of febrile neutropenia-related chemotherapy disruptions ( P= 0.04)
  • Pts hospitalized for pneumonia:
    • Control group = 5/61 (8.1%); median days of hospitalization = 18 (range, 6–22)
    • Peg group = 3/61 (4.9%); median days of hospitalization = 6 (range, 1–21)
    • Peg significantly associated with fewer days of hospitalization due to pneumonia ( P= 0.04)
  • Extra-hematological side effects:
    • Control group = bone pain of ≥grade 3 reported in 6/61 pts (9.8%), treated successfully with paracetamol; 0 pts stopped immune-chemotherapy due to filgrastim related side effects
    • Peg group = grade 3 bone pain reported in 7/61 pts (11.5%), treated successfully with paracetamol; grade 4 bone pain reported in 1 pt (1.6%), who had to discontinue treatment

The authors concluded by stating that in newly diagnosed iNHL after treatment with BR, primary prophylaxis with pegfilgrastim appears to reduce chemotherapy disruptions due to febrile neutropenia and the days of hospitalization. Additionally, they added that pegfilgrastim was advantageous due to its mono-administration, and was well tolerated providing the opportunity of maintaining the planned treatment schedule. Lastly, they stressed that their preliminary results should be validated in controlled clinical trials.


BACKGROUND: In this prospective study, the impact of granulocyte colony-stimulating factors (G-2 CSF) administered during induction treatment with bendamustine plus rituximab for indolent non- Hodgkin Lymphoma (NHL) was evaluated by comparing patients who received secondary prophylaxis with filgrastim (control group) versus. patients who received pegfilgrastim as primary prophylaxis (peg-group). The primary endpoint was the incidence rate of febrile neutropenia (FN)- related chemotherapy disruptions (regarding dose-dense and/or dose-intensity of schedule). The Secondary endpoint included days of hospitalization due to FN, and G-CSF-related side effects (grade ≥3 WHO toxicity criteria) in each group.

METHODS: One hundred twenty-two: 122 consecutive patients, with untreated indolent NHL, were referred to our outpatient unit for remission induction immuno-chemotherapy with bendamustine-rituximab. During the first period, 61 patients received secondary prophylaxis with filgrastim, given "on demand" if ANC was <1000/mm3. During the second period, 61 patients received primary prophylaxis with pegfilgrastim in a single administration.

RESULTS: Pegfilgrastim was significantly associated with fewer incidence rate of FN-related chemotherapy disruptions (11.4% in the control group vs. 1.6% in the peg-group, p = 0.04) and fewer days of hospitalization due to FN (median number 18 days in the control group vs. 6 in the peg-group, p = 0.04). In terms of G-CSF-related extra-hematological grade III side effects, no significant difference has been found in the two groups (9.8% in the control group vs. 11.5% in the peg-group, p = 0.77). Only one patient stopped the treatment in the peg-group due to intolerance.

CONCLUSIONS: In patients with indolent NHL, in front-line treatment with bendamustine plus rituximab, primary prophylaxis with pegfilgrastim seems to reduce the incidence of chemotherapy disruptions due to FN, and the days of hospitalization. Moreover, it is well- tolerated and may increase the opportunity to maintain the planned schedule of treatment. These results make pegfilgrastim an advantageous option in most cases both in terms of cost-effectiveness and quality of life. These preliminary observations need to be validated by controlled clinical trials.

  1. Cerchione C. et al.Pegfilgrastim in primary prophylaxis of febrile neutropenia following frontline bendamustine plus rituximab treatment in patients with indolent non-Hodgkin lymphoma: a single center, real-life experience. Support Care Cancer. 2017 Mar;25(3):839-845. DOI: 10.1007/s00520-016-3468-8. [Epub 2016 Nov 3].