Isavuconazole (ISA) is a newer triazole that has activity against most mold species and has been utilized for prophylaxis as well as treatment in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HSCT). However, several studies have documented breakthrough invasive fungal infections (bIFIs). Thus, we conducted a systematic review and meta-analysis to investigate the incidence of bIFIs among patients receiving ISA prophylaxis.MethodsWe conducted a systematic review and meta-analysis of the published literature using the concept of ISA, HSCT, and HM from 5 search engines. In patients with HSCT and HM, the pooled incidence of bIFI while undergoing ISA prophylaxis was calculated via the DerSimonian-Laird random effect model.ResultsThe systematic review and meta-analysis included 35 and 19 studies, respectively. In total, 991 patients were identified as using ISA prophylaxis, and the majority had either acute myeloid leukemia or myelodysplastic syndrome (69.9%). The pooled incidence of proven/probable bIFI was 7% (95% CI, 4%–12%, I2 = 55%). The most common pathogen was Aspergillus species (43.1%), followed by Candida (22.4%) and Mucorales (12.1%). In 19 studies, mortality rates were documented and ranged between 0% and 100%; the majority of which were >50%.ConclusionsIn patients with HM or HSCT, we found a high incidence of bIFI while undergoing ISA prophylaxis, with high mortality. Given the lack of randomized clinical trials evaluating ISA in this indication, its role in prophylaxis remains unclear.

We investigated infectious complications and the associated risk factors in 181 patients undergoing T-cell engagers for malignancies. Infections were primarily observed in patients with hematological diseases or heavily pre-treated. Mortality due to infectious complications was 2.8%. Concomitant medications with corticosteroids or tocilizumab did not significantly impact the incidence of infections.

While neutropenic enterocolitis (NEC) is a well-known life-threatening complication during intensive chemotherapy, its incidence, impact and outcome on specific at-risk populations remain ill-defined.

Fecal microbiota, live-jslm (RBL; Rebyota), is the first FDA-approved, single-dose, microbiota-based live biotherapeutic to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Patients who are immunocompromised are often considered at higher risk for CDI including recurrence compared to those who are immunocompetent. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated RBL safety and efficacy in participants with rCDI who were considered mildly to moderately immunocompromised.MethodsParticipants with rCDI who had immunocompromising conditions and/or were taking immunosuppressive medications were included. Treatment-emergent adverse events (TEAEs) were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months.ResultsOverall, 793 participants were enrolled in PUNCH CD3-OLS and 697 received RBL; 141 were included in the immunocompromised subgroup. TEAEs within 8 weeks were reported by 44.7% and 48.0% of participants in the immunocompromised and non-immunocompromised subgroups, respectively; most events were mild or moderate gastrointestinal disorders. Serious TEAEs within 8 weeks were reported by 4.3% and 3.8% of participants in the immunocompromised and non-immunocompromised subgroups, respectively. No RBL-related systemic infections occurred. In the immunocompromised subgroup, the treatment success rate at 8 weeks was 75.7% and the sustained clinical response rate at 6 months was 88.7%; similar rates were observed in the non-immunocompromised subgroup (73.3% and 91.6%, respectively).ConclusionsResults of this subgroup analysis of PUNCH CD3-OLS suggest that RBL is safe and efficacious for the prevention of rCDI in participants with mild-to-moderate immunocompromising conditions.Trial registrationNCT03931941

Antibiotic prophylaxis for patients with cancer remains a controversial issue and is not broadly recommended for hematological malignancies. The venetoclax (VEN) and azacitidine (AZA) combination allows for high rates of complete remission in acute myeloid leukemia (AML) but enhances the incidence of febrile neutropenia (FN) compared to AZA alone, making primary antibiotic prophylaxis a relevant question.