Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study’s aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as “probable psychiatric AE (pAE),” if well-characterized neuronal IgG autoantibodies were detected or “possible pAE” (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed

Lymphocytopenia and Anti-CD38 Directed Treatment Impact the Serological SARS-CoV-2 Response after Prime Boost Vaccination in Patients with Multiple Myeloma

Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in PCD patients, as compared to a healthy control group, and on possible influencing factors of serological responses. Blood samples were analyzed for the presence of quantitative anti-SARS-CoV-2 spike RBD Ig. A total of 82 patients were included; 67 received mRNA-, eight vector-based and four heterologous vaccinations. SARS-CoV-2 antibody titers (SP-AbT) were assessed in a mean of 23 days (SD ± 11 days) after the first and in a mean 21 days (SD ± 9) after prime-boost vaccination. A positive SP-AbT was detected in 31.9% of PCD patients after the first vaccination, and in 88.9% (44/49) after prime-boost vaccination, which was significantly less likely than that in the control group (100%, 78/78) (p = 0.008). Furthermore, we have been able to validate our previously suggested threshold of 30 CD19+ B lymphocytes/µL as being predictive for SP-AbT development. Despite anti-CD38 directed therapy, quadruplet treatment, higher age and missing deep remission, which correlated negatively with SP-AbT appearance, SP-AbT formation is possible in a majority of myeloma patients after prime-boost vaccination

Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial

Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR 2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55–89) years, with a median GFR of 20.1 mL/min/1.73 m2 (interquartile range, 9.4–27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1–10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI

Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial

Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression