Infection Risk Associated with Daratumumab

Abstract

BackgroundDaratumumab is an IgG kappa monoclonal antibody (mAB) against CD38 which is expressed on myeloma cells. It has recently been approved for treatment of patients with relapsed refractory multiple myeloma. Our objective was to identify the potential infectious complications associated with daratumumab use.MethodsWe conducted a retrospective analysis of myeloma patients who received daratumumab at our institution from October 2015 to December 2016. Patients were divided into four groups based on administration regimen of daratumumab: (1) single agent with dexamethasone; (2) triple therapy with proteasome inhibitor (PI), immune-modulating drug (IMiD), mitogen-activated protein kinase (MEK) inhibitor or mAB; (3) quadruple therapy with IMiD + PI ± mAB or cyclophosphamide; (4) with high-dose chemotherapy. For each group, we evaluated the incidence of infection, neutropenia (defined as ANC <1,000), hospitalization, and 90-day survival.ResultsA total of 171 patients (63% male, 37% female) were included in the study and received a total of 343 cycles of daratumumab. Median age was 68 years. A total of 151 infections occurred in 121 of the 343 cycles (40% bacterial; 52% viral). There was a significant association between development of infection and chemotherapy regimen used (χ2 = 17, P ≤ 0.001). Patients developed neutropenia in 129 of 254 cycles (51%). There was a significant association between the development of neutropenia and chemotherapy regimen used (χ2 = 43.51, P < 0.00001). Discontinuation of chemotherapy occurred in 65 cycles (19%), mainly due to progression of disease (54%). Eighty subjects (23%) required hospitalization, infection being the main cause (51%). Ninety-day survival was 91.8%.ConclusionInfection is common among myeloma patients who receive daratumumab. Myeloma patients who receive daratumumab in conjunction with multidrug chemotherapy regimens have an increased risk of infection and neutropenia. Because daratumumab is given predominantly as outpatient therapy, a greater understanding of the potential immunomodulatory effects of daratumumab will lead to increased vigilance in identifying and treating clinically significant infections.Disclosures F. Davies, Janssen: Consultant, Speaker honorarium. G. Morgan, Janssen: Consultant and Research Contractor, Research support and Speaker honorarium.

Daratumumab for the treatment of refractory ANCA-associated vasculitis

“…Rituximab is known to induce a delayed response, and time between rituximab and daratumumab was short in patient 2 due to the dynamic worsening of his disease. While we did not observe significant adverse events, daratumumab treatment was associated with an increased risk of infection in systematic studies for multiple myeloma 16 and in case reports in autoimmune diseases. 9 17 Prospective clinical trials will be needed to investigate the safety and efficacy of daratumumab in AAV and to identify patients who could benefit from a plasma celltargeting drug.…”

Infections in Patients with Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

“…Daratumumab has the following effects: neutropenia, lymphopenia, hyperglycemia, and decrease in natural killer cells, which play a major role in the immune clearance of virally infected cells [125,126]. The use of daratumumab in the treatment of MM patients is associated with the following infections: nasopharyngitis, pneumonia, and viral infections such as VZV [125][126][127][128].…”

Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma

“…The side-effect profile is well established, with common side effects including infusion related reactions. More important are the cytopenias and infections associated with daratumumab, with one study reporting a total of 11.7% of patients requiring hospitalizations due to infections in 171 patients treated with daratumumab with and without chemotherapy [ 19 ]. However, these infections were generally manageable with antivirals and antibiotics.…”