Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma

• Published in: PloS one 2019-02, Vol.14 (2), p.e0211927-e0211927
• Main Authors: Nahi, Hareth, Chrobok, Michael, Gran, Charlotte, Lund, Johan, Gruber, Astrid, Gahrton, Gösta, Ljungman, Per, Wagner, Arnika Kathleen, Alici, Evren
• Format: Article
• Language: English
• Subjects: Activation; Adult; Adverse drug reactions; Aged; Aged, 80 and over; Antibacterial agents; Antibodies; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antiviral agents; Bacterial Infections - chemically induced; Bacterial Infections - immunology; Biology and life sciences; CD38 antigen; Cell-mediated immunity; Chicken pox; Chickenpox; Cohort Studies; Complications; Complications and side effects; Cytomegalovirus; Cytotoxicity; Daratumumab; Depletion; Development and progression; Disease; Disease susceptibility; Dosage and administration; Drug therapy; FDA approval; Female; Health aspects; Hematology; Herpes simplex; Herpes viruses; Herpes zoster; Herpesvirus infections; Hospitals; Humans; Immunity; Immunoglobulin G; Immunotherapy; Infection; Infections; Infectious diseases; Killer cells; Killer Cells, Natural - immunology; Lymphocyte Depletion; Lymphocytes; Male; Medicin och hälsovetenskap; Medicine; Medicine and health sciences; Middle Aged; Monoclonal antibodies; Mortality; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - immunology; Multiple Myeloma - microbiology; Multiple Myeloma - virology; Natural killer cells; Patients; Prophylaxis; Respiratory syncytial virus; Risk factors; Stem cells; Targeted cancer therapy; Transplants & implants; Varicella; Viral infections; Virus Diseases - chemically induced; Virus Diseases - immunology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0211927

Treatment with Daratumumab (Dara), a monoclonal anti-CD38 antibody of IgG1 subtype, is effective in patients with multiple myeloma (MM). However, Dara also impairs the cellular immunity, which in turn may lead to higher susceptibility to infections. The exact link between immune impairment and infectious complications is unclear. In this study, we report that nine out of 23 patients (39%) with progressive MM had infectious complications after Dara treatment. Five of these patients had viral infections, two developed with bacterial infections and two with both bacterial and viral infections. Two of the viral infections were exogenous, i.e. acute respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), while five consisted of reactivations, i.e. one herpes simplex (HSV), 1 varicella-zoster (VZV) and three cytomegalovirus (CMV). Infections were solely seen in patients with partial response or worse. Assessment of circulating lymphocytes indicated a selective depletion of NK cells and viral reactivation after Dara treatment, however this finding does not exclude the multiple components of viral immune-surveillance that may get disabled during this monoclonal treatment in this patient cohort. These results suggest that the use of antiviral and antibacterial prophylaxis and screening of the patients should be considered.