Characteristics and incidence of infections in patients with multiple myeloma treated by bispecific antibodies: a national retrospective study on the behalf of G2I and Intergroupe Francophone du Myélome.

OBJECTIVES: Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed. METHODS: A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration. RESULTS: Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19). DISCUSSIONS: The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.

Diagnostic, clinical management, and outcome of bone flap-related osteomyelitis after cranioplasty.

OBJECTIVES: We aimed to describe diagnostic, management, and outcome of bone flap-related osteomyelitis after cranioplasty. METHODS: Patients followed up in our tertiary care hospital for bone flap-related osteomyelitis after cranioplasty were included in a retrospective cohort (2008-2021). Determinants of treatment failure were assessed using logistic regression and Kaplan-Meier curves analysis. RESULTS: The 144 included patients (81 [56.3%] males; median age 53.4 [interquartile range [IQR], 42.6-62.5] years) mostly presented wound abnormalities (n = 115, 79.9%). All infections were documented, the main pathogens being Staphylococcus aureus (n = 64, 44.4%), Cutibacterium acnes (n = 57, 39.6%), gram-negative bacilli (n = 40, 27.8%) and/or non-aureus staphylococci (n = 34, 23.6%). Surgery was performed in 140 (97.2%) cases, for bone flap removal (n = 102, 72.9%) or debridement with flap retention (n = 31, 22.1%), along with 12.7 (IQR, 8.0-14.0) weeks of antimicrobial therapy. After a follow-up of 117.1 (IQR, 62.5-235.5) weeks, 37 (26.1%) failures were observed: 16 (43.2%) infection persistence, three (8.1%) relapses, 22 (59.5%) superinfections and/or two (1.7%) infection-related deaths. Excluding superinfections, determinants of the 19 (13.4%) specific failures were an index craniectomy for brain tumor (odds ratio = 4.038, P = 0.033) and curettage of bone edges (odds ratio = 0.342, P = 0.048). CONCLUSION: Post-craniectomy bone flap osteomyelitis are difficult-to-treat infection, necessitating prolonged antimicrobial therapy with appropriate surgical debridement, and advocating for multidisciplinary management in dedicated reference centers.

Prognosis and factors associated with disseminated nocardiosis: a ten-year multicenter study.

OBJECTIVES: Nocardiosis is a rare opportunistic infection that is frequently associated with dissemination (i.e. involvement of several body sites). Identifying the factors associated with Nocardia spp. dissemination may help improving the management of patients with nocardiosis. METHODS: This 10-year (2010-2020) retrospective multicenter cohort study included adult patients with Nocardia-confirmed infections. The first objective was to determine the factors associated with disseminated nocardiosis. The secondary endpoints were to determine and compare the management and the 12-month overall mortality in patients with localized and disseminated nocardiosis. Univariate and multivariate logistic regression analyses were used. RESULTS: Nocardia spp. infection was confirmed in 110 patients, of whom 38 (34.5%) had disseminated nocardiosis. In univariate analysis, the factors associated with dissemination were immunosuppressive conditions: having an auto-immune disease and receiving high-dose corticosteroid (31.5% vs 8.3%, P = 0.003 and 52.6% vs 26.3%, P = 0.007, respectively). Absolute lymphocyte count <1 G/L at diagnosis was the only biomarker associated with dissemination (57.2% vs 26.3%, P = 0.007). Nocardia farcinica was not only the most frequent species identified in patient specimens (n = 22, 20%) but was also associated with a higher rate of dissemination (36.8% vs 11.1%, P = 0.002). Multivariate analysis confirmed the association between auto-immune diseases, lymphopenia, N. farcinica species and the higher rate of dissemination. Even though patients with disseminated nocardiosis were treated longer and more often with an antibiotic combination therapy, their 12-month overall mortality was significantly higher than that of patients with localized nocardiosis (36.8% vs 18%). CONCLUSIONS: Dissemination of Nocardia spp. is favoured by auto-immune diseases, lymphopenia, and infection with N. farcinica.

Long-term use of liposomal nebulized amikacin and tedizolid for the treatment of disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation.

Nocardiosis is a life-threatening opportunistic infection in immunocompromised patients. Herein, we present successful adjunctive use of liposomal nebulized amikacin and tedizolid in a recipient of allogeneic hematopoietic stem cell transplantation infected with Nocardia nova complex who presented multiple complications to conventional therapeutic options.