Increased Risk of Leukemia Associated with an Autoimmune Disease Treatment

Researchers reporting at the American Society of Hematology (ASH) annual meeting in San Diego this week highlight a study that shows autoimmune disease patients receiving the immunosuppressive drug azathioprine, have a seven-fold increased risk of acute myeloid leukemia and myelodysplastic syndromes.

The study of 40,011 patients who were seen at Mayo Clinic in Arizona and Florida, confirmed 86 cases of autoimmune diseases with myelodysplastic syndromes (MDS) in 55 patients, 21 patients in the early stages of acute myeloid leukemia (AML) and 10 patients with a history of acute myeloid leukemia.

The development of myeloid neoplasms (MN) after treatment for an autoimmune disease is of increasing concern among physicians. But whether a myeloid neoplasm will occur depends on a number of variables:  type of autoimmune disease; whether it is associated with a chronically activated inflammatory cascade known to be associated with an increased risk of myeloid malignancy and, the effects of other disease modifying therapies.

“The addition of therapeutic agents for treatment of autoimmune diseases theoretically amplifies the opportunity for myeloid neoplasms to develop in genetically susceptible individuals,” the researchers wrote in their conference presentation. The study presented at ASH examines the association of cytotoxic, anti-inflammatory and immune-modulating agents to treat autoimmune disease as risk factors for developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).

The most common autoimmune profiles includes rheumatoid arthritis at 26.4 percent, psoriasis at 20.7 percent and systemic lupus at 13.8 percent. The average patient was 72 years old, 57 percent of which were male. The median onset of autoimmune disease to diagnosis of a myeloid neoplasm was six years (1-54 year range).

While 12.8 percent of these patients received no treatment, the patients who were treated with oral or intravenous therapies had similar exposures for immune-modulating agents (33.7% and 37.8% respectively) and cytotoxic therapies, such as chemotherapy and radiotherapy  (47.7 and 44.8% respectively). And, 57 out of 86 cases (66.3%) received either a cytotoxic or immune-modulating agent.  By comparison, 105 out of 172 (61.1%) controls received either agent; p=0.495.

“Azathioprine was the only statistically significant agent exposure observed more frequently in the study cohort than controls with an OR of 7.05 (p= < 0.001). There was no increased incidence of MDS or AML in TNF-antagonist treated patients. No significant correlation for duration of agent exposure by drug category was observed,” the researchers reported in their conference abstract.

Methotrexate, the first line of defense for rheumatoid arthritis and other autoimmune diseases, and mercaptopurine, and mycophenolate reported favorable odd ratios, but they were not statistically significant. Nor were associations found for anti-TNF agents, the second line of defense in autoimmune disorders.

The findings were reported by Natalie Ertz-Archambault, M.D., of Mayo Clinic in Arizona.

Disclosures:

Disclosures: Dueck: Bayer: Honoraria. Mesa: Gilead: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Incyte Corporation: Research Funding; Galena: Consultancy; Ariad: Consultancy; CTI: Research Funding; Promedior: Research Funding. Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

References:

Natalie Ertz-Archambault, et al. "Myelodysplastic Syndromes and Acute Myelogenous Leukemia Resulting from Therapy for Autoimmune Disease, a Case-Control Cohort Study of 40,011 Patients," American Society of Hematology annual meeting. Dec. 3- 6, 2016.