Susman, David

Abstract Sporadic late‐onset nemaline myopathy (SLONM) associated with monoclonal protein (MP) is a rare disease with an aggressive, and often fatal course. Whether SLONM + MP represents a malignancy or dysimmune disease remains unclear. Currently, two main approaches are used to treat SLONM + MP: nonchemotherapy‐based treatment (immunosuppression, intravenous immunoglobulins, plasmapheresis and plasma exchange) or chemotherapy with or without autologous stem cell transplantation. Due to the rare occurrence of the disease, the best treatment modality is unknown. We analyzed treatment and outcomes in a large cohort of 53 patients with SLONM + MP: four our own patients and 49 cases from published literature. Neurological improvement in the nonchemotherapy group (N = 25) was observed in 52% of patients: 8% reached marked improvement, 8% moderate response, 36% mild response; none reached complete remission (CR). In the chemotherapy group (N = 28), neurological improvement was seen in 86% of patients: 46% reached CR, 25% marked response, 11% moderate response and 4% mild response. The best neurological improvement correlated with deep hematological remission. Mean time to best response in the chemotherapy group was 8 months versus 21 months in the nonchemotherapy group ( P < .001). Overall survival was higher in patients in the chemotherapy group. A chemotherapy approach should be the preferred treatment for patients with SLOMN + MP with the goal to reach complete hematologic remission. Based on the clinical, morphological peculiarities, aggressive disease course and superior clinical benefits of chemotherapy over nonchemotherapy, SLONM + MP should be considered as a hematological malignancy with the presence of MP of clinical rather than undetermined significance.

8545 Background: A subset of sporadic late-onset nemaline myopathy (SLONM) associated with monoclonal gammopathy of undetermined significance (MGUS) has more aggressive course, often fatal. Whether SLONM+MGUS is a malignancy or dysimmunity is unclear. Two approaches are used to treat SLONM+MGUS: 1) immunosuppression (IS) ± plasmapheresis/exchange; 2) chemotherapy (ChT) ± autologous stem cell transplantation (ASCT). Due to the rare occurrence of the disease the best treatment modality is not known. Methods: We conducted a literature search to identify previous treatment for patients with SLONM+MGUS using PubMed, Elsevier, Medline, and CINAHL databases from 1975 to 2019. All publications were carefully reviewed to remove “duplicate” patients. Overall, 28 reports were included for the final analysis. Results: 38 unique patients with SLONM+MGUS received either IS (n = 19) or ChT ± ASCT (n = 19). The median age was 48 years [24-75]. In the IT group 74% (n = 14) were males vs 53% (n = 10) in the ChT group. All patients had IgG monoclonal protein (MP): kappa in 57% (n = 11) in the IT, 42% (n = 8) in the ChT group. In the IT group MP values were 0.42 & 0.2 g/L (n = 2); in the ChT group median MP was 2.7 g/L [0.1-14, n = 14]. In the IT group 84% (n = 16) received steroids, 26% (n = 5) plasmapheresis, 53% (n = 10) non-steroid immunosuppressants, 11% (n = 2) rituximab, and 53% (n = 10) IVIG. Six patients (32%) had one IT modality; 13 (68%) had 2 or 3. In the ChT group 10 patients (53%) had ASCT; 6 patients (31%) had CyBorD or Lenalidomide+Dexamethasone + ASCT; 3 patients (16%) had chemotherapy without ASCT. 10 patients in IT group had neurological improvement (NI): 53% overall response (OR) with 16% (n = 3) complete remission (CR), and 37% (n = 7) partial response (PR). No improvement/progression had 9 patients (47%). In 2 patients (10%), neurological CR was associated with resolution of MP. Mean time to best response was 19 months. In ChT group 18 patients achieved NI: 94.7% OR with CR in 73.7% (n = 14) and PR in 21.0% (n = 4). Only one patient had no response to therapy. The best NI correlated with resolution of MP. Mean time to best response was 10 months. Conclusions: Our study with the most extensive cohort of patients with SLOMN+MGUS supports ChT ± consolidative ASCT aimed at complete elimination of the malignant plasma cell clone as the preferred treatment. Superior clinical benefits of ChT suggest that the presence of MP has clinical rather than undetermined significance, and SLOAN + MP should be considered as a malignancy rather than dysimmunity.