Infection risk with immunomodulatory and proteasome inhibitor-based therapies across treatment phases for multiple myeloma: A systematic review and meta-analysis

Abstract

Background: The objective of this review was to determine the impact of immunomodulatory drugs (IMiDs) and proteasome inhibitor (PI)-based therapy on infection risk in patients with myeloma across three treatment periods: induction, maintenance therapy and relapse/refractory disease (RRMM).

Methods: A systematic review and meta-analysis of randomised controlled trials (RCT) of IMiD and PI-based therapy versus conventional therapy from 1990 to 2015 using MEDLINE, EMBASE and CENTRAL was conducted. Study methods, characteristics, interventions, outcomes and rate of infection were extracted using a standardised tool.

Findings: Thirty RCTs of 13,105 patients fulfilled inclusion criteria. The rate of severe infection with the use of IMiD-based therapy was 13.4%, 22.4%, 10.5% and 16.6% for induction therapy for non-transplant- and transplant-eligible patients, maintenance therapy and therapy for RRMM, respectively. Rate of severe infection with PI-based induction in transplant-eligible patients was 19.7%. Compared to conventional therapy, use of IMiD-based induction therapy was associated with reduced risk for transplant patients (RR 0.76, p < 0.01). There was no significant difference with PI-based therapy. For maintenance therapy and RRMM, use of IMiD-based therapy was significantly associated with 74% and 51% increased risk of severe infection, respectively. Compared to thalidomide, bortezomib-based induction therapy and lenalidomide maintenance therapy were associated with increased risk of severe infection (RR 2.03, p < 0.01; RR 1.95, p = 0.03).

Interpretation: The differential impact of myeloma therapies on risk for infection and the effect of treatment phases upon risk have now been established. Thalidomide is associated with the lowest risk of severe infection when used for induction and maintenance therapy.

Funding: Fight Cancer Foundation.

Keywords: Immunomodulatory therapy; Infection; Myeloma; Risk; Systematic review.