Introduction: Patients with multiple myeloma are at higher risk for infections due to disease pathogenesis and administered therapies. Infection is a significant cause of morbidity and the leading cause of death in patients (pts) with newly diagnosed multiple myeloma (NDMM). The risk of infection may be associated with neutropenia, hypogammaglobulinemia, and NK cell depletion. Daratumumab is approved for NDMM or relapsed/refractory multiple myeloma (RRMM). The use of daratumumab (dara) has improved patient outcomes but has changed the frequency and epidemiology of infections. The overall risk of infection with daratumumab treatment is around 38%, being upper respiratory tract infections the most common.The purpose of this study was to evaluate the number, the type and risk of infection events (IE) associated with the use of dara in patients with NDMM in the induction phase of transplant eligible and transplant ineligible NDMM patients.
Methods: We retrospectively evaluated 308 pts with NDMM treatment in 8 Italian Hematology Centers who underwent induction therapy based on dara-bortezomib, thalidomide and dexamethasone (D-VTD), dara-lenalidomide and dexamethasone (D-Rd) and dara-bortezomib and dexamethasone (D-VMP) between 2020 and 2023..
Results: Overall, 105/308 (34%) developed an infection of any grade, 30/105 in D-VTD, 61/105in D-Rd and 14/105 in D-VMP arm. There was no difference on antiviral and antimicrobial prophylaxis in the 3 treatment groups. The median time to infection events was similar between the 3 groups D-VMP 161 days (104-243), D-Rd 156 days (97-370) and D-VTD 82 days (44-184) (p=0.064). Type of IE were upper respiratory tract infection in 81/105 pts (77%), SARS-COV2 infection 12/105 pts (11%), herpes simplex and varicella zoster virus (VZV) in 2/105 pts (1.9%), abdominal infection 3/105 pts (2.8%) and infection of urinary tract 2/105 pts (1.9%) of any grade. No differences were present in the grade and in the duration of IE. In all groups a statistically significant reduction was seen in the IgA level at the time of the IE (p=0.006), while no differences were present for IgG and IgM level in 3 treatment group. Moreover, a significant difference in neutropenia (p=0.002) and lymphocytophenia pre and post IE (p=0.006) resulted in all three groups. In our experience, no significant differences were found between the three treatment groups in terms of incidence, type and degree of infections, while significant differences were found between baseline IgA levels, neutropenia and lymphopenia at the time of the IE.
Conclusions: A larger patient cohort and further studies are warranted to confirm these data and to identify patients at higher risk for infection, understanding the potential benefit of infectious prophylaxis in the clinical management in this setting of NDMM.
