Biologic Drugs and Malignancy: A Literature Review Examining the Impact of Concomitant Immunosuppressive Medications

Abstract

The objective of this work was to conduct a systematic review of the frequency with which concomitant immunosuppressive medication(s) are used in patients receiving biologics who develop malignancy. We conducted a PubMed search using the term “malignancy” and specific cancers combined with “biologic” and specific biologic drug names to identify case reports and case series written in English documenting patients who were diagnosed with malignancy while being treated with a biologic agent. Demographic information, biologic medication including treatment indication, malignancy type, time to malignancy diagnosis, patient outcome, and information regarding concomitant usage of immunosuppressive medication(s) were recorded. A total of 210 patients from 78 case reports and 21 case series met inclusion criteria and were evaluated. Among patients who developed malignancy while on biologic therapy, 64.8% were simultaneously being treated with ≥1 other immunosuppressive medication. A median time of 12 months was observed between initiation of biologic therapy and development of disease in this cohort. Methotrexate (28.6%) and azathioprine (23.8%) were the most common concomitant therapies. When compared with patients receiving biologic monotherapy, patients who received biologics with other immunosuppressive medications experienced 3.21 times more deaths because of malignancy with an odds ratio of 2.12 (95% CI, 1.07–4.19). The risk of malignancy among patients receiving biologic therapy is significantly confounded by the prevalent use of concomitant immunosuppressive medication(s). This risk may be overestimated, particularly for patients who take biologic drugs as monotherapy.