Abstract 4225: Myelodysplastic syndrome and acute myeloid leukemia following use of chemo-immunotherapy and granulocyte colony-stimulating factors among elderly non-Hodgkin lymphoma patients
Authors: Moran Kellyn M. , Wu Zhaoju , Adimadhyam Sruthi , Lee Todd A. , Chiu Brian C. , Calip Gregory S. 
Published: August 2018

Purpose The purpose of this study was to examine use of granulocyte colony-stimulating factors (G-CSF) in relation to risk of myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) in a population-based cohort of elderly patients with non-Hodgkin lymphoma (NHL).

Methods We conducted a retrospective cohort study of adults ages 66 years and older diagnosed with first primary NHL between 2001 and 2011 using the Surveillance Epidemiology and End Results (SEER)-Medicare linked database. Patients were included if they were alive and without documented secondary primary cancer at three months post-diagnosis.

Using a validated algorithm with Medicare claims and SEER records, we identified MDS/AML cases, primary NHL treatment received (i.e., chemo-immunotherapy and radiation) and type and number of doses of G-CSF received (i.e., filgrastim and/or pegfilgrastim). We determined the risk of developing MDS/AML at 12 months or longer after NHL diagnosis. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for MDS/AML risk associated with G-CSF use in cause-specific Cox proportional hazards models, stratified by treatment to account for confounding by indication.

Results A total of 18,245 patients were included with a mean age of 76 years and median follow up of 3.5 years. Most patients were diagnosed with diffuse large B-cell lymphoma (34%) and follicular lymphoma (22%). Fifty-six percent of all patients received chemo-immunotherapy, among whom most received rituximab-based chemotherapy (74%) or monotherapy (18%). G-CSF was most commonly used among those who received rituximab plus chemotherapy (77%). Subsequent MDS/AML was observed in 666 (3.7%) patients. Overall, we found a modest increased risk of MDS/AML with any use of G-CSF (HR=1.28, 95% CI 1.01-1.62); although, a linear trend was observed with increasing number of G-CSF doses (P&lt;0.001). Among patients receiving rituximab plus chemotherapy, risk of MDS/AML was highest in those receiving 10 or more G-CSF doses (HR=1.64, 95% CI 1.14-2.37). When analyzing specific G-CSF agents, this increased MDS/AML risk was consistently observed with filgrastim (10+ doses: HR=1.67, 95% CI 1.25-2.23), but not with pegfilgrastim (10+ doses: HR=1.11, 95% CI 0.84-1.45).

Conclusions In this study of elderly NHL patients, we observed a higher MDS/AML risk among those receiving chemo-immunotherapy and G-CSF that was specific to higher number of filgrastim doses but not pegfilgrastim. The benefits of preventing complications from therapy-related neutropenia in patients receiving highly myeloablative treatments likely outweigh the risk of this rare but serious second primary cancer. Understanding differential risk by type of agent warrants further study with the increasing use of G-CSF and FDA-approved biosimilar products (filgrastim-sndz) newly available.

Citation Format: Kellyn M. Moran, Zhaoju Wu, Sruthi Adimadhyam, Todd A. Lee, Brian C. Chiu, Gregory S. Calip. Myelodysplastic syndrome and acute myeloid leukemia following use of chemo-immunotherapy and granulocyte colony-stimulating factors among elderly non-Hodgkin lymphoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4225.