Impact of daratumumab on anti-HLA antibodies level in patients with multiple myeloma

Abstract Daratumumab, a humanized anti-CD38 monoclonal antibody, has demonstrated anti-plasma cell activity alone and in combination with other drugs in multiple myeloma (MM) and in light chain amyloidosis (AL). Allogenic anti-Human leukocyte antigen (HLA) antibodies are frequently encountered in patients awaiting kidney transplantation, complicating the access to a compatible transplant and represent a major risk factor of humoral rejection. Durably removing the antibodies or eliminating the producing cells is an objective that is currently out of reach. The objectives of our study were to evaluate the frequency of anti-HLA antibodies in MM and AL patients, and to determine the effect of daratumumab on them. Eligible patients with diagnosed MM or AL were selected (n = 182), among whom 84 had anti HLA antibodies (46%). Forty-nine patients (45 MM and 4 AL) were retrospectively included. Patients were treated with a combination of an alkylating agent, an immunomodulatory imide drug (IMiD), a Proteasome inhibitor, with (n = 22) or without (n = 22) daratumumab. Five patients received daratumumab alone. Treatment with daratumumab lowered anti-HLA antibodies in 85% (23/27) of cases including complete loss in 56% of cases (15/27) compared to 77% (17/22) and 45% (10/22) respectively, p = 0.8. This study couldn’t find a statistic impact of daratumumab to lower HLA antibody in this cohort. The association with chemotherapy could be an important bias and this hypothesis will be evaluated in ongoing studies enrolling patients undergoing kidney transplantation.