Cytomegalovirus and Epstein-Barr Virus Infection during Daratumumab Treatment in Patients with Multiple Myeloma

Background: Daratumumab (Dara) is a monoclonal antibody targeting CD38, which has been wildly used in the treatment of multiple myeloma (MM). It was observed that patients treated with Dara-containing regimes had a relatively high rate of infections. Here, we included 53 patients with MM who were treated with Dara-containing regimes and reviewed 13 cases of MM patients with EBV and/or CMV infections during the treatment.

Method: We retrospectively analyzed the clinical data of 53 patients with MM treated with Dara-containing regimes at the First Affiliated Hospital of Zhejiang University from December 2018 to May 2022. The CMV-DNA and EBV-DNA loads in the blood were regularly monitored before the initial Dara-containing regimes and every time of Dara infusions by real-time quantitative PCR. We further detected the phenotypic characteristics of the lymphocytes in peripheral blood (PB) with multiple-color flow cytometry. The gating strategy of CD4⁺T cells, CD8⁺ T cells, B cells, and NK cells were executed as CD3⁺CD4⁺, CD3⁺CD8⁺, CD3^-CD19⁺, and CD3^-CD56⁺, respectively. Disease-related factors between the different groups were compared using the chi-squared test for categorical variables, and the Mann-Whitney U test for continuous variables.

Results:

We observed that 13/53 (24.53%) patients had CMV and/or EBV infections during Dara-containing treatments (4 with EBV infection alone, 7 with CMV infection alone, and 2 with dual infection).

Albumin and the absolute number of lymphocytes in PB were significantly lower in patients with CMV and/or EBV infections. No significant differences were observed in disease type, disease relapse, ISS stage, the ratio of free light chain, plasma cells in bone marrow, high-risk cytogenetic changes, prior treatments, and combined drugs with Dara.

The median time of infections from the first Dara infusion was 27 days. 7 cases with CMV infections were treated with ganciclovir (300mg bid intravenous for 2 weeks; 500mg tid po until CMV-DNA turned negative on 2 consecutive measurements) in combination with IVIG (400 mg/kg qd 5 days; 10 g biw maintenance until 1 week after DNA undetectable). 1 patient with dual infection and 4 patients with EBV infection alone were treated with IVIG alone. Another patient with dual infection received no treatment. The median duration of viremia was 34 days.

The subpopulations of lymphocytes in PB were repeat detected in 32 patients (2 with single EBV infection, 6 with single CMV infection, 1 with dual inflection, 23 without infection). In longitudinal analysis of the subpopulations of lymphocytes in PB, we observed NK cell and B cell depletion, and T cell expansion (especially CD8⁺T cell) after the treatment of Dara. Compared with patients without CMV and/or EBV infections during Dara-containing regimes, patients with CMV and/or EBV infections had significant lower absolute numbers of NK cells, total T cells, CD8⁺T cells at 1 month and absolute numbers of CD8⁺T cells at 2 months after the first Dara infusion.

Conclusion: We observed a considerable risk of infections of EBV and/or CMV in the early stage of Dara treatment in patients with MM and speculated the potential involvements of NK cells depletion and CD8⁺T cells expansion in the occurrence of EBV and CMV infections.

No relevant conflicts of interest to declare.