Protracted viral infections in patients with multiple myeloma receiving bispecific T-cell engager therapy targeting B-cell maturation antigen
Breanna Palmen, Parameswaran Hari, Anita D’Souza, Muhammad Bilal Abid
Abstract
Recent expansion in therapeutic landscape in multiple myeloma (MM) has resulted in significant improvement in patient survival.Specifically, chimeric antigen receptor (CAR) T-cells and bispecific T-cell engagers (BiTEs) targeting B-cell maturation antigen (BCMA) have resulted in unprecedented response rates 1 .While infections remain the leading cause of morbidity and mortality in patients with relapsed/refractory multiple myeloma (RRMM) 2 , the on-target-off-tumor toxicities associated with BCMA-targeting agents lead to prolonged B-cell aplasia, hypogammaglobulinemia, and increase the cumulative risk for infections [3][4][5][6] .Currently, two CAR T-cells and one BiTE product targeting BCMA are approved by the Food and Drug Administration (FDA) for the treatment of RRMM.Patients receiving these agents, either in clinical trials or commercially, need to have received several prior lines of treatment often including autologous hematopoietic cell transplant (autoHCT), monoclonal antibodies, and have prolonged cytopenia.This further intensifies the net state of immunosuppression, superimposed upon the immunoparesis with myeloma.Prior studies in BCMA CAR-T highlighted an infection rate ranging between 23%-63% 3,4,[7][8][9] .A single center study examined infections upto 1 year post CAR-T in 55 patients and showed that 53% of infections were viral, 40% bacterial, and 6% fungal 9 .Another single-center study in 104 patients with RRMM and NHL undergoing BCMA and CD19-directed CAR-T showed that BCMA CAR-T recipients had significantly more viral infections than CD19-directed CAR-T recipients 10 .While there are evolving data among BCMA CAR-T cell recipients, evidence remains limited among BCMA BiTE recipients.In a single-center analysis of MM patients receiving BCMA CARs (n=26) and BiTEs (n=36), CAR-T recipients had higher baseline absolute lymphocyte counts (ALC) and were less heavily pretreated.The cumulative incidence and burden of infections was higher among BCMA BiTEs compared to BCMA CAR-T