Citations

ABSTRACT This review provides an in-depth analysis of glucocorticoid therapy for lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus that affects up to 51.7% of patients. LN significantly increases the risk of mortality and progression to end-stage kidney disease. Glucocorticoids have been central to LN treatment for decades due to their anti-inflammatory properties, but optimal dosing strategies remain uncertain. The review discusses the historical evolution of glucocorticoid use, highlighting the shift from high-dose regimens to combined approaches with immunosuppressants and lower glucocorticoid doses to minimize adverse effects. Mechanistically, glucocorticoids exert effects through genomic and non-genomic pathways, modulating immune responses and metabolism. Long-term use is associated with risks such as infection, osteoporosis, hyperglycemia and cardiovascular disease. The review examines different dosing strategies, including intravenous pulse therapy and oral regimens, and presents evidence of their efficacy and safety. It also explores alternative approaches, such as low-dose and glucocorticoid-free regimens, which show promise but require further study. The review concludes by emphasizing the need for future research to optimize glucocorticoid regimens, refine tapering protocols and identify safer therapeutic combinations, as glucocorticoids remain a cornerstone in LN management despite their challenges.

ABSTRACT We report a case of acute interstitial nephritis (AIN) in a 68-year-old male with squamous cell carcinoma (SCC) and relapsed/refractory multiple myeloma (RRMM) who developed acute kidney injury (AKI) shortly after starting teclistamab for RRMM. Despite stable renal function on immune checkpoint inhibitor (ICI) therapy for SCC, proton pump inhibitors and trimethoprim-sulfamethoxazole for 3 years, AKI only occurred post-teclistamab initiation. Biopsy-confirmed AIN with serum creatinine improved only after pulse-dose steroids. This case highlights a potential synergistic nephrotoxic effect of teclistamab and ICIs, warranting further investigation into teclistamab's renal safety.

OBJECTIVE Endovascular intracranial aneurysm (IA) management has significantly evolved over the last 2 decades. Despite these advancements, the aneurysm recanalization rate after coil embolization remains a concern. Statins have been found to affect vascular repair and remodeling; therefore, the authors hypothesized that patients receiving statin therapy at the time of coil embolization would have lower aneurysm recurrence and retreatment rates compared with patients not receiving statin therapy. METHODS A post hoc analysis was conducted of the primary data from patients enrolled in the Hydrogel Endovascular Aneurysm Treatment Trial focusing on the impact of statin use on the recurrence rates of 3- to 14-mm IAs after endovascular coiling. The primary outcome measured included aneurysm recurrence over 18–24 months using the Raymond-Roy Occlusion Classification. Secondary outcomes included major and minor recurrence rates and retreatment rates. Propensity score matching based on patient and aneurysm characteristics was performed to mitigate selection bias. RESULTS A total of 577 patients with data on statin use were eligible for this analysis. Of these, 178 (30.8%) patients were using statins and 399 (69.2%) were not. After propensity score matching, 156 (39.2%) patients were included in the statin group and 242 (60.8%) in the nonstatin group. The recurrence rate was 3.8% (6/156) in the statin group and 10.7% (26/242) in the nonstatin group (p = 0.013). In a subgroup analysis, statin use significantly reduced recurrence in patients with unruptured aneurysms (1.6% vs 9.7%, p = 0.005), but not in those with ruptured aneurysms (12.5% vs 13.6%, p = 0.876). CONCLUSIONS Statin use was associated with a reduced rate of aneurysm recurrence in patients who underwent endovascular coiling for IAs with a decreased rate of retreatment during the follow-up period. Statins are a relatively low-risk treatment and may be an effective therapy to reduce recanalization of IAs, although further prospective studies are warranted to validate these findings.

PURPOSE Teclistamab is initiated with a step-up dosing (SUD) schedule to mitigate the risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Early teclistamab users commonly received SUD in a hospital setting. This study aimed to evaluate safety and health care resource utilization (HRU) in real-world patients with multiple myeloma who initiated teclistamab SUD in an outpatient setting. METHODS This was a retrospective study using Mayo Clinic's electronic medical records from October 26, 2022, to October 31, 2023. Patient characteristics were summarized for all patients treated with teclistamab and separately for patients who started SUD outpatient. SUD pattern, safety, HRU, and post-SUD dosing schedule were described in patients with complete SUD. RESULTS At data cutoff, 65 patients received ≥1 teclistamab dose, including 58 patients who initiated SUD outpatient (median age, 69.2 years; male, 63.8%; White, 89.7%). Among 57 patients who completed SUD in an outpatient setting, all received premedications on the days of teclistamab administrations per label recommendation; 18 (31.6%) developed CRS (13 grade 1, four grade 2, and one grade 4) and two developed ICANS (one each with grade 2 and 4). All CRS and ICANS resolved with supportive care and all patients continued treatment. Eighteen patients were admitted to the hospital for CRS treatment, with a median CRS-related hospital stay of 2 days per admission. Most (60%) doses during SUD required <1 hour clinic time between administration and checkout. Post-SUD, clinic time for treatment doses decreased to <30 minutes for most doses (82%). CONCLUSION Outcomes of this study support outpatient administration as a safe and feasible option for teclistamab SUD to potentially reduce HRU and improve patient experiences.

Abstract Nocardiosis is an uncommon yet potentially devastating infection. Nocardia tends to affect individuals with chronic lung disease or immunocompromising conditions, 2 groups increasing in number. Incidence of nocardiosis is likely to increase as well, and it is vital to have an approach to this complex disease. Here, we aim to review the presentation, diagnosis, and management of Nocardia in the modern era. We will also highlight areas of uncertainty in our understanding of nocardiosis and propose a general approach to nocardiosis therapy, accounting for response and tolerance of Nocardia treatment.

Abstract The antiapoptotic protein, myeloid cell leukemia-1 (Mcl-1), contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models. This dose escalation study evaluated voruciclib in patients with previously treated hematologic malignancies. Initially, voruciclib was administered daily, continuously, on a 28-day cycle (group 1). After 2 patients with prior allogeneic stem cell transplantation had a dose-limiting toxicity (DLT) of interstitial pneumonitis at 100 mg, voruciclib administration was changed to days 1 to 14 of a 28-day cycle (group 2). Forty patients, 21 with AML and 19 with B-cell malignancies, were enrolled. Patients had a median of 3 prior lines of therapy (range, 1-8). Dose escalation in group 2 was stopped at 200 mg, a dose that achieved plasma concentrations sufficient for target inhibition, without DLTs observed. The most common adverse events were diarrhea (30%), nausea (25%), anemia (22%), fatigue (22%), constipation (17%), dizziness (15%), and dyspnea (15%). In AML, 1 patient achieved a morphologic leukemia-free state, and 2 had stable disease. Voruciclib treatment led to a decrease in MCL1 messenger RNA expression, downregulation of myelocytomatosis (MYC) and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase 2. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax for patients with previously treated AML. This trial was registered at www.clinicaltrials.gov as #NCT03547115.