MT-3724, a novel engineered toxin body comprised of an anti-CD20 single-chain variable fragment genetically fused to Shiga-like Toxin A subunit, is capable of binding to and internalizing against CD20, inducing cell killing via permanent ribosomal inactivation. This study evaluated MT-3724 in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/rNHL). This open-label, multiple-dose phase Ia/b trial included a dose escalation in patients with r/rNHL according to a standard 3+3 design. Primary objectives were to determine the MTD and pharmacokinetics/pharmacodynamics. In a dose expansion study at MTD in serum rituximab-negative patients with diffuse large B-cell lymphoma (DLBCL), primary objectives were safety, tolerability, and pharmacokinetics/pharmacodynamics. Twenty-seven patients enrolled. MTD was 50 μg/kg/dose with 6,000 μg/dose cap. Thirteen patients experienced at least one grade ≥3 treatment-related adverse events; the most common grade ≥3 event was myalgia (11.1%). Two patients (75 μg/kg/dose) experienced grade 2 treatment-related capillary leak syndrome. Overall objective response rate was 21.7%. In serum rituximab-negative patients with DLBCL or composite DLBCL (n = 12), overall response rate was 41.7% (complete response, n = 2; partial response, n = 3). In patients with detectable baseline peripheral B cells, treatment resulted in dose-dependent B-cell depletion. The proportion of patients with anti-drug antibodies (ADA) increased during treatment and the majority appeared to be neutralizing based on an in vitro assay; nevertheless, tumor regression and responses were observed. MT-3724 demonstrated efficacy at the MTD in this population of previously treated patients with r/rDLBCL, with mild-to-moderate immunogenic safety events.Significance: This work describes the safety and efficacy of a new pharmaceutical pathway that could provide a treatment option for a subset of patients with a critical unmet therapeutic need. The study drug, MT-3724, is capable of targeting B-cell lymphomas via a unique, potent cell-killing mechanism that appears to be promising.

Andrés Gómez-De León, Andres Noyola-Pérez, Lourdes Gil-Flores, Hemant Malhotra, Vasile Musteata, Amal Mohamed El-Beshlawy, Hilman Tadjoedin, Carolina Pavlo Andrés Gómez-De León, Andres Noyola-Pérez, Lourdes Gil-Flores, Hemant Malhotra, Vasile Musteata, Amal Mohamed El-Beshlawy, Hilman Tadjoedin, Carolina Pavlo

Introduction. Primary myelofibrosis is a rare myeloproliferative neoplasm that affects 0.2-1.5 people per 100,000. As a rule, the diagnosis is confirmed after 60 years, but recently, hematologists around the world have encountered the problem of primary myelofibrosis in young people. The classic manifestations of myelofibrosis are characterized by splenomegaly, cytopenia, and bone marrow fibrosis, but in patients younger than 40 years, the diagnosis is most often made in the prefibrotic stage of the neoplasm. The aim of the paper is to identify and evaluate the clinical and hematological features of primary myelofibrosis in young patients in the prefibrotic stage. Material and methods. A retrospective study was performed on clinical cases of primary myelofibrosis, registered at the Oncological Institute of the Republic of Moldova. The diagnosis was confirmed according to 2016 WHO criteria based on histological and molecular studies. We enrolled young patients under the age of 40 who had been diagnosed with prefibrosis in our study and analyzed them for clinical manifestations and complete blood count parameters. To optimize the analysis, all patients were divided into two groups according to their age: 18–29 and 30–40 years old. Results. Changes in the complete blood count, manifested by thrombocytosis and leukocytosis, are the main laboratory patterns of primary myelofibrosis in young patients in the prefibrotic stage. The most relevant clinical features are splenomegaly and hepatomegaly, but no correlation between these manifestations has been found. Conclusions. The classical clinical and hematological characteristics of primary myelofibrosis do not specify lowand intermediate-risk patients’ management in the prefibrotic stage, as compared with the other chronic myeloproliferative BCR-ABL-negative neoplasms. The proliferation type of primary myelofibrosis is characteristic for young patients with pre-fibrotic stage. According to our results, the main manifestations in the prefibrotic stage are detected in a complete blood count and comprise anemia, leucopenia, leukocytosis, and thrombocytosis.

The increase of incidence in the working-age population, commonly late diagnosis and signifi cant levels of disability in non-Hodgkin’s lymphomas (NHL) may be considered as key topics of clinical hematooncology and public health management. An analytical study was performed – the narrative review of the literature under the form of a synthesis article. To achieve this goal, we searched by keywords for medical scientifi c publications in the database Google Search, PubMed, Z-library, NCIB, Medscape, Hinari. The incidence of NHL in Western countries is 14–19 new cases per 100000 of population (4% of all malignancies). In both sexes, the incidence of NHL corresponded to the country-related Human Development Index. The incidence rates at the beginning of the last decade varied signifi cantly by geographic region, being higher in males. In 2016, 2017, 2018, 2019 and 2020 the incidence of NHL (C82 - C85; C88, С96) in Moldova was 5.9, 6.7, 5.1, 6.8 and 5.1, exceeded the respective index in other hematological malignancies, but manifested the decreasing tendency. NHL caused 6.8 million DALYs (disability-adjusted life-years) in 2016, with 98% coming from lost-life years and 2% from years lived with disabilities. Th e primary determinants of costs were hospitalizations (aggressive NHL – 44%, indolent NHL – 50% of total costs) and outpatient visits.