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Cyclophosphamide tied to ‘relatively small’ lymphoma risk among patients with lupus
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Patients with systemic lupus erythematosus who took immunosuppressive medications did not necessarily increase their risk for lymphoma, and those exposed to cyclophosphamide had only a relatively low rate of incidence, according to study results.
In case-cohort analyses within a multisite systemic lupus erythematosus (SLE) cohort, researchers studied 75 patients with lymphoma (mean age at entry, 45.2 years; 80% women) and 4,961 cancer-free patients (mean age, 38.5 years; 90.9% women). Regression models generated adjusted hazard ratios for lymphoma, time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs and glucocorticoids), demographics, calendar year, Sjögren’s syndrome, SLE duration and disease activity.
Sasha Bernatsky
Seventy-five lymphomas (non-Hodgkin’s, n=72; Hodgkin’s, n=3) occurred a mean of 12.4 years after SLE diagnosis, and 54 were of B-cell origin. Lymphoma risk for SLE was greater in men than women and increased with age, which mimicked the general population. There was no clear association of disease activity with lymphoma risk, based on unadjusted (HR=0.62; 95% CI, 0.34-1.13) and fully adjusted (HR=0.68; 95% CI, 0.36-1.29) analyses.
“There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls,” the researchers reported.
“Most of the lymphoma cases in the SLE patients that we studied had not been exposed to immunosuppressive drugs prior to their lymphoma occurring,” researcher Sasha Bernatsky, MD, PhD, FRCPC, of the division of clinical epidemiology, Research Institute at the McGill University Health Centre, Quebec, told Healio.com. “However, we did find a suggestion of an increase in lymphoma risk after one drug, cyclophosphamide. Still, the absolute number of lymphomas among subjects exposed to cyclophosphamide was relatively small [less than 0.1% per year], and the drug remains currently important for very severe SLE manifestations.
“Our study addresses long-standing fears (on the part of patients and practitioners] of a link between lupus medication and cancer. The fear of developing cancer among lupus patients has been so great that some patients may be reluctant to take their medication and others may stop all together.”
Perspective
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Harry S. Jacob, MD, FRCPath(Hon)
Since cyclophosphamide has been shown to diminish likelihood of end-stage renal disease in lupus, these studies imply that risk–benefit analysis favors the use of this immunosuppressive in most lupus patients.
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