Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study

摘要

Background: Daratumumab (Dara) is generally well tolerated, but is associated with increased risk of infection. Methods: We investigated hypogammaglobinemia occurrence in different Dara-based regimens. Multiple myeloma (MM) patients were treated with ?2 cycles of Dara-based therapy during 2016–2020, mainly for relapsed/refractory disease. Data on patient characteristics, treatment regimens, polyclonal IgG (poly-IgG) and uninvolved free light chain (Un-FLC) levels during treatment, as well as predictors for hypogammaglobinemia and predictors for infections, were evaluated retrospectively. Results: A total of 84 patients, median age 67.2?years, were included. Dara, mainly as ?2 line therapy (88.1%, n?=?74), was combined with immunomodulating drugs (IMiDs) (53%), proteasome inhibitors (PIs) (15%), IMiDs-PIs (11%), or dexamethasone only (21%). Median treatment duration was 13?months. Median Poly-IgG levels at 0, 2, and 4?months were 7.1?g/l, 4.5?g/l, and 4?g/l, respectively, and remained low throughout treatment. Lower poly-IgG pre-Dara ( p?=?0.001) and Dara-PIs (±IMiDs) regimen were associated with lower poly-IgG levels at 4?months ( p?=?0.03). Only patients treated with Dara monotherapy had partial immune reconstitution, reflected by resumption of IgM levels. Most (85%) patients developed ?1 infections, mostly grade 1–2 respiratory (76%). A lower poly-IgG level post Dara (RR?=?1.137 p?=?0.026) predicted increased risk of any infection. Intravenous immunoglobulin (IVIG) was associated with a significant decrease in all infections. Conclusion: Relapsed MM patients treated with Dara, often experience persistent hypogammaglobinemia, irrespective of responsiveness to treatment. Infections, especially respiratory, are frequent and apparently related to low Poly-IgG levels. IVIG should be considered for reducing infections in these patients.