In an animal model of bleomycin-induced lung toxicity, filgrastim increased alveolar neutrophil recruitment, pulmonary edema, and lung myeloperoxidase activity. That finding led to concerns about whether filgrastim could increase pulmonary toxicity when used together with adriamycin, bleomycin, vinblastine, and dacarbazine regimens.
Treatment with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) has become the standard of care in treating Hodgkin lymphoma (HL), but in an animal model of bleomycin-induced lung toxicity, filgrastim increased alveolar neutrophil recruitment, pulmonary edema, and lung myeloperoxidase activity. That finding led to concerns about whether filgrastim could increase pulmonary toxicity when used together with ABVD, and there is as yet no clear consensus on managing patients with HL when they require filgrastim.
A study recently published in the International Journal of Hematology-Oncology and Stem Cell Research sought to evaluate whether there is evidence of an increased risk of pulmonary toxicity in patients with HL who receive chemotherapy regimens including bleomycin in combination with filgrastim.
The researchers conducted a single-center retrospective analysis of 54 patients with HL who had received at least 1 dose of bleomycin between January 2003 and July 2015, and they performed chart reviews to identify pulmonary toxicity during the period starting from the day of the first dose of bleomycin until 1 year after the first dose. Of the 54 total patients, 21 received bleomycin alone and 33 received bleomycin plus filgrastim. The median number of days to administration of G-CSF after the first dose of bleomycin was 14 (range, 0-153).
In total, 10 patients met criteria for pulmonary toxicity, and all cases of pulmonary toxicity occurred within the first 9 months after the start of treatment. Of the 10 patients who met the criteria, 3 patients had received bleomycin alone and 7 had received a combination of bleomycin and filgrastim. The difference between these groups was not statistically significant (P = .50). The crude hazard ratio for development of pulmonary toxicity for the bleomycin plus filgrastim cohort was 1.58 (95% CI, 0.41-6.81).
The researchers concluded that their study showed no evidence that the combination of bleomycin and filgrastim increases the risk of pulmonary toxicity and that, “For patients who do not meet white blood cell count parameters on the day of subsequent planned treatment or just prior to subsequent treatment, we recommend administering one dose of [filgrastim] at 5 mcg/kg in order to maintain dose intensity of chemotherapy for this patient population.”
Additionally, patients who develop febrile neutropenia should receive filgrastim with subsequent cycles of treatment to minimize the duration of neutropenia. However, the authors add that pegfilgrastim, with its longer duration of action, should be avoided in this patient population because of the short interval between chemotherapy doses.
Binder AF, Rai S, Steinberg A. The use of filgrastim in patients with Hodgkin lymphoma receiving ABVD. 2017;11(4):286-292. Int J Hematol Oncol Stem Cell Res. PMCID: PMC5767288.