Chafic Karam

Introduction/Aims: Chimeric antigen receptor T‐cell (CAR‐T) therapy has transformed the management of refractory hematologic malignancies, but neurologic complications remain a major concern. While immune effector cell‐associated neurotoxicity syndrome is well recognized, peripheral neuropathies such as neuralgic amyotrophy have rarely been described. Methods: We characterize the clinical, electrophysiologic, and imaging features of neuralgic amyotrophy after B‐cell maturation antigen (BCMA)‐directed CAR‐T therapy at a single tertiary care center. Results: We identified four patients with neuralgic amyotrophy following BCMA‐directed CAR‐T therapy, corresponding to 1.5% of total patients treated in that time. Patients developed acute bilateral shoulder pain followed by weakness 8–12 days after CAR‐T infusion. Manifestations included scapular winging and arm weakness, with electromyography showing denervation most prominently in the muscles supplied by the long thoracic and suprascapular nerves. Corticosteroid use appeared to be associated with symptomatic improvement, although residual weakness persisted in most. Diagnosis was delayed in three patients due to misattribution of symptoms to other causes. Discussion: Neuralgic amyotrophy may represent an underrecognized complication of BCMA‐directed CAR‐T therapy. The consistent timing of onset, bilateral involvement, and responsiveness to corticosteroids support an inflammatory mechanism. Clinicians should maintain vigilance for this complication, as prompt recognition and treatment may mitigate long‐term neurological morbidity.

Key terms describing the activity status and clinical outcomes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) lack standardized definitions. To address the need for uniform definitions, we sought to develop formal consensus-based terminology to define key aspects pertinent to the management of CIDP. In April 2025, the GBS|CIDP Foundation International convened a Task Force of 17 international CIDP experts, 2 guest experts from related specialties, and 3 patient representatives. Task Force panels iteratively reviewed, discussed, and voted on proposed definitions for No Evidence of Disease Activity, Relapse, Response, Refractory, Remission, and Residual Symptoms. Relevant literature was reviewed to inform each definition. A modified Delphi approach was used to achieve consensus, defined as a median rating ≥7 on a 9-point scale with ≥80% agreement. Voting included 17 content experts and 3 patient representatives. Guest experts provided nonvoting input. Composite metrics incorporating disability, strength impairment, and patient perception were determined to provide the most sensitive and specific assessment of clinical change in CIDP. Using commonly used clinical outcome measures, including minimally clinically important differences where available, unique definitions were developed for each clinical term. Definitions for No Evidence of Disease Activity, Relapse, Response (minimal, partial, and optimal), Refractory, Remission, and Residual Symptoms were iteratively refined to integrate patient-reported experiences, standardized disability scores, and objective measures of strength impairment, ensuring that each term captured a multidimensional view of disease status. The development of consensus-based definitions for key clinical terms in CIDP addresses a longstanding gap in standardizing the assessment of disease activity and treatment outcomes. By combining patient-reported experiences with objective disability and strength measures, the Task Force created comprehensive definitions reflecting the patient experience. The iterative Delphi process ensured broad expert agreement while allowing patient perspectives to inform the terminology. These standardized definitions may improve consistent evaluations in clinical practice, facilitate communication among healthcare providers, and support more robust design and interpretation of clinical trials. Furthermore, the incorporation of composite metrics sensitive to meaningful clinical changes may enhance the ability to detect treatment effects and disease progression, ultimately promoting more precise and patient-centered management of CIDP.

The therapeutic landscape for systemic immunoglobulin light chain (AL) amyloidosis has been revolutionized by daratumumab-based regimens, achieving 76% 5-year overall survival in the landmark ANDROMEDA trial. However, the current prognostic models were developed using patient populations treated with now-suboptimal therapies, creating a critical gap between risk stratification models and contemporary outcomes. This comprehensive review analyzes prognostic factors and progression biomarkers in AL, categorizing them into disease-specific (clone-related and organ-related) and patient-specific factors. Notably, traditional baseline biomarkers including difference between involved and uninvolved free light chains and bone marrow plasma cell burden are losing prognostic significance with effective clone-directed therapies. Emerging approaches show promise, including dynamic markers such as minimal residual disease by free light chain mass spectrometry, cardiac imaging parameters such as global longitudinal strain, and functional measures. There is an urgent need for validation studies and prognostic model refinement to identify patients at high risk who may benefit from interventions beyond anti–plasma cell therapy.

Introductions/Aims: The clinical utility of serum neurofilament light chain (sNfL) in the evaluation and management of peripheral neuropathy (PN) remains poorly defined. This study aimed to evaluate the utility of sNfL for diagnosing PN, assessing disease activity, and monitoring treatment response using a commercially available assay. Methods: This was a retrospective cohort study at the University of Pennsylvania between June 2024 and March 2025. Patients with, or at risk for, PN who underwent sNfL testing were included. Demographics, PN etiology, clinical findings, and sNfL levels were analyzed. Results: One hundred and twenty‐eight patients were included: 41 with chronic inflammatory demyelinating polyneuropathy (CIDP), 36 with transthyretin amyloidosis (ATTR), 13 with vasculitic PN, 13 with Charcot–Marie–Tooth disease (CMT), 6 with multifocal motor neuropathy (MMN), 4 with anti‐MAG neuropathy, 4 with Guillain‐Barré syndrome (GBS), and 11 with other PN types. Of these, 113 had definite large fiber PN; 14 were asymptomatic TTRv carriers, and one had small fiber neuropathy. Elevated sNfL levels were observed in 31 patients (24%). The odds ratio of having elevated sNfL in treatable vs. non‐treatable PN was 28.33 (95% CI: 5.04–159.18). Among CIDP and ATTRv‐PN patients, sNfL was most often elevated in treatment‐naïve or refractory cases and decreased with treatment. Discussion: Routine sNfL testing is warranted in selected patients with PN, such as treatment‐naïve or refractory CIDP, active vasculitic PN, and ATTRv‐PN. Elevated sNfL in patients with PN should prompt evaluation for a potentially treatable cause and may offer useful adjunctive information to support clinical decision‐making.

Background/Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a progressive and fatal disease with >130 known underlying variants in the TTR gene. We describe the utility of two no-charge genetic testing programs in identifying TTR variants in participants across Europe/Middle East and North America, respectively. Methods: Eligible adult participants in GeneAct^® and Alnylam Act^® had a family history or clinical suspicion of ATTRv. Testing was performed using gene panels for neuropathies or cardiomyopathy, or a single-gene TTR test. Diagnostic yield was defined as one pathogenic/likely pathogenic variant in TTR. Results: Overall, 2713 and 89,760 participants were tested in GeneAct^® and Alnylam Act^®. Genetic diagnosis was established in 95 and 4297 participants, respectively, resulting in a diagnostic yield of 3.5% and 4.8%. V122I (p.V142I) was the most common variant, identified in 34 of these participants in GeneAct^® and 3299 in Alnylam Act^®. Cardiac and neurologic signs/symptoms were the most common manifestations across both programs, as reflected in the specialties ordering tests in Alnylam Act^® (cardiology, 29.1%; neurology, 31.5%). Conclusions: These data highlight the importance of genetic testing for early identification of ATTRv, especially among patients with cardiac and neuropathy symptoms. Genetic testing has the potential to improve diagnostic timeframes and outcomes in ATTRv.

The purpose of this review is to give an update on myelin-associated glycoprotein (MAG) neuropathy. There are several recent developments in anti-MAG neuropathy, with the major one being the retrospective analysis of 50 clinical trials that showed that at least a 50% reduction in anti-MAG levels is associated with a therapeutic response. Other updates address antibody levels needed for a positive test, response, and exacerbations to therapy and the type of antibody more associated with malignancy. Anti-MAG neuropathy is heterogeneous, and the natural history of the disease continues to be refined. Treatment options are being explored for refractory disease.