Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors.

OBJECTIVE: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. One-year follow-up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1-year survival. RESULTS: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One-year survival was 51.9% (41/79). PML-immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death-1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow-up magnetic resonance imaging at least once during follow-up (OR = 3.16, 95% confidence interval = 1.20-8.72, p = 0.02) was associated with 1-year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1-month follow-up in survivors compared to nonsurvivors (p < 0.0001). Thirty-two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%). INTERPRETATION: In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML-IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257-270.

Infectious risk when prescribing rituximab in patients with hypogammaglobulinemia acquired in the setting of autoimmune diseases.

We conducted a single-centre retrospective cohort study in a French University Hospital between 2010 and 2018 to describe the risk of severe infectious event (SIE) within 2 years after the date of first rituximab infusion (T0) prescribed after the evidence of acquired hypogammaglobulinemia (gamma globulins [GG] ≤ 6 g/L) in the setting of autoimmune diseases (AID) other than rheumatoid arthritis. SIE occurred in 26 out of 121 included patients. Two years cumulative incidence rates were 12.7 % (95 % CI 5.1-23.9) in the multiple sclerosis/neuromyelitis optica spectrum disorder group (n = 48), 27.6 % (95 % CI 15.7-40.9) in the ANCA-associated vasculitis group (n = 48) and 30.6 % (95 % CI 13.1-50.3) in the 'other AID' group (n = 25). Median GG level at T0 was 5.3 g/l (IQR 4.1-5.6) in the 'SIE' group and 5.6 g/l (IQR 4.7-5.8) in the 'no SIE' group (p = 0.04). In regression analysis, risk of SIE increased with Charlson comorbidity index ≥ 3 (OR 2.77; 95 % CI 1.01-7.57), lung disease (OR 3.20; 95 % CI 1.27-7.99), GG < 4 g/L (OR 3.39; 95 % CI 1.02-11.19), concomitant corticosteroid therapy (OR 4.13; 95 % CI 1.63-10.44), previous cyclophosphamide exposure (OR 2.69; 95 % CI 1.10-6.61), a lymphocyte count < 1000 cells/µL (OR 2.86; 95 % CI 1.12-7.21) and absence of pneumococcal vaccination (OR 3.50; 95 % CI 1.41-8.70). These results may help to inform clinical decision when considering a treatment by rituximab in immunosuppressed AID patients with hypogammaglobulinemia.

A severe monkeypox infection in a patient with an advanced HIV infection treated with tecovirimat: clinical and virological outcome.

A patient aged 28 years who is immunocompromised and living with HIV/AIDS became infected with the monkeypox virus (MPXV). His clinical condition deteriorated for 37 days, with fever, skin lesions, and diarrhea before going to the infectious diseases department, where his severe, protracted infection was treated with tecovirimat for 14 days. His condition rapidly improved, and the skin lesions decreased, as did the MPXV loads, with no adverse events. This case indicates that tecovirimat might be effective for treating patients who are immunocompromised and are infected with MPXV.

Pulmonary mucormycosis following autologous hematopoietic stem cell transplantation for rapidly progressive diffuse cutaneous systemic sclerosis: A case report.

RATIONALE: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc). PATIENT CONCERNS: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT. DIAGNOSES: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample. INTERVENTIONS AND OUTCOMES: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up. LESSONS: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.