Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

Abstract

Background & aims: Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy for these patients. Published studies have been small with few events, precluding robust estimates of risk.

Methods: We searched Medline, EMBASE, and conference proceedings for terms related to immune-mediated disease, immune-suppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of patients with inflammatory bowel disease, and 1 of patients with psoriasis) and stratified studies by type of immune-suppressive therapy (monoclonal antibodies to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no immune suppression). A random-effects meta-analysis was performed to calculate the pooled incidence rates as well as risk differences between the various treatments.

Results: Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow-up evaluation after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8 per 1000 p-y), immune-modulator therapy (36.2 per 1000 p-y), or no immunosuppression (37.5 per 1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5 per 1000 p-y) (P > .1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease showed similar results, with no increase in risk. We found similar pooled incidence values for new or primary cancers when immunosuppression was initiated within 6 years (33.6 per 1000 p-y for immune-modulatory agents and 43.7 per 1000 p-y for anti-TNF agents) vs more than 6 years after the index cancer (32.9 per 1000 p-y for immune-modulatory agents, P = .86; and 21.0 per 1000 p-y for anti-TNF agents, P = .43).

Conclusions: In a meta-analysis of 16 studies, we observed similar rates of cancer recurrence among individuals with prior cancer who received no immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination treatments. Prospective studies are needed to ascertain optimal intervals for re-initiation of immune-suppressive therapies for individuals with specific cancers.

Keywords: IBD; Immunosuppression; Lymphoma; Melanoma.

Figure 1

Flowchart of the literature search

Figure 2

Forest Plot of Risk of recurrence of cancer or development of new primary by type of immunosuppression in individuals with a prior history of cancer IBD – inflammatory bowel disease; RA – rheumatoid arthritis; NMSC – non-melanoma skin cancer

Figure 3

Forest Plot of Risk of new primary cancer by type of immunosuppression in individuals with a prior history of cancer

Figure 4

Forest Plot of Risk of recurrence of prior cancer by type of immunosuppression in individuals with a prior history of cancer

Figure 5

Incident rate differences between no-immunosuppression, conventional immunomodulator and anti-TNF therapy (a) Conventional IMM vs. anti-TNF therapy (b) Conventional IMM vs. no IS (c) Anti-TNF vs. no IS

Figure 5

Incident rate differences between no-immunosuppression, conventional immunomodulator and anti-TNF therapy (a) Conventional IMM vs. anti-TNF therapy (b) Conventional IMM vs. no IS (c) Anti-TNF vs. no IS

Figure 5

Incident rate differences between no-immunosuppression, conventional immunomodulator and anti-TNF therapy (a) Conventional IMM vs. anti-TNF therapy (b) Conventional IMM vs. no IS (c) Anti-TNF vs. no IS