Citations

Abstract Varlilumab is a monoclonal antibody with agonistic activity on CD27. The efficacy of single-agent PD-1 inhibitors on aggressive B-cell non-Hodkin lymphoma is limited. Preclinical and phase 1 data suggest that Varlilumab is safe and may have synergistic activity with PD-1 inhibitors. In the DIAL study, we explored whether dual immunomodulatory therapy with Varlilumab and Nivolumab in patients with relapsed/refractory aggressive B-NHL was safe and effective. We conducted a randomized phase II clinical trial on adult patients with relapsed/refractory aggressive B-NHL. Patients were randomized to receive Nivolumab monotherapy in the control group and Varlilumab combined with Nivolumab in the experimental group. Crossover to the experimental group was allowed upon progression in the control group. The primary endpoint was the overall response rate based on the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). 54 patients underwent randomization, and 51 received assigned intervention and were included in the intention-to-treat analysis. Objective response was observed in 6 out of 51 patients (ORR 12%). There were 4 responders (ORR 16%) in the Nivolumab group and 2 responders (ORR 7.6%) in the Nivolumab and Varlilumab combination group (p = 0.3). None of the 7 patients that crossed over to the experimental group responded to the addition of Varlilumab. The ORR of patients who were previously exposed to CAR-T cell therapy was 13% (5 out of 39) compared to 8.3% (1 out of 12) in the unexposed patients (p > 0.99). The rate of treatment emergent adverse events was similar between groups, and there was no fatal TEAE in the study. The addition of Varlilumab to Nivolumb did not improve outcomes in patients with aggressive B-NHL. Even though this trial was not designed to evaluate immunotherapy as a rescue therapy after CAR-T failure, most patients (76%) had previously received CAR-T therapy, and their outcomes were equally poor.

BACKGROUND Intraneural perineuriomas (INPs) are rare benign peripheral nerve sheath tumors with characteristic clinical and MRI features. Their 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) appearance has not been characterized in a patient series. The authors evaluated FDG uptake patterns in INP. OBSERVATIONS The authors retrospectively reviewed that data of patients with confirmed INP who had MRI and FDG PET studies that included the affected nerve. Eight patients were included (5 male and 3 female; mean age 30.8 years, range 16–61 years). All lesions showed mildly increased FDG uptake relative to the contralateral nerve (lesion maximum standardized uptake value [SUVmax]: mean 1.5, median 1.2, range 1.1–3.5; contralateral nerve SUVmax: mean 0.9, median 0.9, range 0.8–1.0) and skeletal muscle background (SUVmean: mean 0.8, range 0.5–0.9). Six patients had denervation edema and/or fatty atrophy, without appreciably increased FDG uptake in the affected musculature. No additional abnormal hypermetabolic foci were identified. LESSONS INPs generally demonstrate low-level FDG uptake. PET is best regarded as a complementary test when already available or when metabolic characterization may refine the differential diagnosis; unexpectedly high uptake should prompt reconsideration of the diagnosis or additional evaluation. https://thejns.org/doi/10.3171/CASE26698

BACKGROUND Hypertrophic olivary degeneration (HOD) is a rare form of transsynaptic degeneration caused by disruption of the dentato-rubro-olivary pathway (Guillain-Mollaret triangle). It is most described following surgical intervention or acute hemorrhagic injury affecting that pathway. However, longitudinal imaging documenting the natural progression of HOD in patients with brainstem cerebral cavernous malformations (CCMs) remains sparsely described at the individual patient level. OBSERVATIONS The authors present the case of a 70-year-old woman with a pontine CCM followed longitudinally over 4 years. Initial imaging demonstrated a right-sided pontine lesion with unilateral HOD in the absence of symptoms. Over time, the CCM enlarged and extended across the midline, coinciding with the development of bilateral HOD and delayed onset of gait imbalance and palatal myoclonus. No surgical intervention was performed. LESSONS In this case, the radiographic evolution from unilateral to bilateral involvement occurred concurrently with the delayed clinical manifestation of HOD. https://thejns.org/doi/10.3171/CASE26577