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Filgrastim use increases risk for myelodysplastic syndrome, AML in non-Hodgkin lymphoma

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February 19, 2019

Use of the granulocyte colony-stimulating factor filgrastim appeared associated with a higher risk for myelodysplastic syndrome and acute myeloid leukemia among older patients with non-Hodgkin lymphoma, according to results of a retrospective study published in Cancer.

Researchers did not, however, observe this association with pegfilgrastim.

“Older patients with [non-Hodgkin lymphoma] are represented less in clinical trials with long-term follow up; therefore, information on treatment risks and surveillance for rare adverse events like myelodysplastic syndrome/AML in patients aged 65 years and older are answered only by large, population-based cohort studies like this,” Gregory S. Calip, PharmD, MPH, PhD, of the center for pharmacoepidemiology and pharmacoeconomic research at University of Illinois at Chicago, and colleagues wrote. “Furthermore, our study captured a period when both filgrastim and pegfilgrastim products were available for use.”

Calip and colleagues used the SEER-Medicare-linked database to evaluate the relationship between use of these granulocyte colony-stimulating factors and the risk for myelodysplastic syndrome and AML among 18,245 patients aged 65 and older (median age, 76.2 years; 54.3% women; 85.2% non-Hispanic white) diagnosed with first primary non-Hodgkin lymphoma between 2001 and 2011.

More than half of the patients (56%) received chemotherapy and/or immunotherapy.

Seventy-seven percent of patients treated with rituximab (Rituxan; Genentech, Biogen) in combination with multiple chemotherapy regimens used a granulocyte colony-stimulating factor.

Researchers followed patients until the first day of myelodysplastic syndrome or AML diagnosis, development of a different second primary cancer, relapse treatment for non-Hodgkin lymphoma or death.

Median follow-up was 3.5 years.

Results showed 666 patients (3.7%) developed either myelodysplastic syndrome or AML. Researchers observed a modest increased risk for these second primary cancers with receipt of granulocyte colony-stimulating factor (HR = 1.28; 95% CI, 1.01-1.62), a risk that increased with increasing doses (P for trend < .01).

In analyzing specific agents, researchers observed increased risk for myelodysplastic syndrome or AML with 10 or more doses of filgrastim (HR = 1.67; 95% CI, 1.25-2.23) but not with pegfilgrastim (HR = 1; 95% CI, 0.84-1.24).

Limitations included a lack of complete information on granulocyte colony-stimulating factor dosing schedules or intensity.

Researchers wrote that the reason behind the difference in risks with filgrastim and pegfilgrastim are unclear.

“Understanding possible differences in the long-term safety of granulocyte colony-stimulating factors is extremely important with biosimilar products now entering the market,” Calip and colleagues wrote. “Further studies of myelodysplastic syndrome/AML risk after treatment for non-Hodgkin lymphoma should include all age groups and biosimilar drugs to confirm and fully characterize the risk attributable to specific granulocyte colony-stimulating factor agents.” – by John DeRosier


Disclosure s : Calip reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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