Kinetics of Humoral Immunodeficiency With Bispecific Antibody Therapy in Relapsed Refractory Multiple Myeloma

Abstract

This case series describes the kinetics of humoral deficiency in patients with relapsed refractory multiple myeloma treated with bispecific antibodies, the infectious complications, and response to COVID-19 immunization.

Infectious complications of bispecific antibody therapy in patients with multiple myeloma

“…A trial of T cell/FCRH5 BsAb reported grade ≥3 infection of 19% and limited data is available for NK targeting BsAb [3,9]. Real world data on rates of hypogammaglobulinaemia, impact of immunoglobulin replacement, and associated rates of infection are starting to emerge, however more evidence is necessary [10,11].…”

Recommendations on prevention of infections during chimeric antigen receptor T‐cell and bispecific antibody therapy in multiple myeloma

“…In addition to the lack of universal uptake of COVID-19 vaccination, suboptimal vaccines response has been demonstrated in recipients of CAR T-cell and BsAb therapy. 26,52 Additionally, COVID-19 remains a significant concern to patients with MM with mortality as high as 14% in recipients of BCMA directed T-cell therapy. [53][54][55] Given the high rate of US COVID19 infection, and reasonable uptake of vaccination in some geographical areas, high titers of COVID19 neutralizing antibodies are now reported in IVIG products.…”

“…Additionally, BCMA is essential for survival of long‐lived plasma cells, further explaining profound plasma cell aplasia seen with BCMA‐targeted therapies 25 . Notably, both BsAb and CAR T‐cell therapy led to profound and prolonged hypogammaglobulinemia 26,27 . In the pivotal KarMMa trial (idecabtagene vicleucel/ide‐cell, CAR T‐cell), any‐grade hypogammaglobulinemia was reported in 5% of patients at ≤8 weeks, 16% of patients at >8 weeks and ≤6 months, and 2% of patients at >6 months 6 .…”

“…A significant proportion (76%) of patients have hypogammaglobinemia after BCMA CAR T‐cell therapy and a third of patients remain on IVIG supplements at 9–12 months after CAR T‐cell infusion 40 . With BCMA BsAb therapy, nearly every responding patient develop hypogammaglobinemia, and this is compounded by the continuous nature of therapy with BsAb 26,41 . Additionally, 50% of relapsed refractory MM patients have baseline hypogammaglobulinemia at the time of initiation of these therapies.…”

Protracted viral infections in patients with multiple myeloma receiving bispecific T-cell engager therapy targeting B-cell maturation antigen

“…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] .…”