Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma.

Ixazomib is approved for use in combination with lenalidomide and dexamethasone (IRd) for patients with multiple myeloma (MM) who received at least one previous therapy. Registration study "TOURMALINE MM-1" was published in 2016. Nevertheless, clinical trials are significantly different from real-world use. From June 2016 to December 2018, IRd was available for Slovak patients with relapsed/refractory MM through a Named Patient Program. The aim of this study was to evaluate the efficacy and safety of ixazomib. We analyzed in this cohort study outcomes of 106 MM patients treated with IRd at 2 academic centers. The median age at diagnosis was 63 years (44-78). The median number of prior lines was 2 (1-7). The majority had high international staging system (ISS) score: 18, 29, and 59 were in the ISS I, ISS II, and ISS III groups, respectively. Treatment continued until progression, unacceptable toxicity, or death. The median follow-up for the entire cohort was 29 (0-49) months. The overall response rate was 74.5% (complete remission, 7.5%; partial remission, 67%). The median overall survival was not reached. Median progression-free survival (PFS) was 43 months (95% CI 35.6-50.4). The Kaplan-Meier method was used to generate survival curves, and we compared the influence of different factors on PFS. The most common hematological adverse events of any grade were neutropenia (90.4%), anemia (55.6%), and thrombocytopenia (43.4%). Our real-world data support the use of IRd as a highly effective and well-tolerated oral treatment protocol for relapsed myeloma.

Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia.

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. >2 prior treatments, with equally good effectivity in standard-risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.

[Idiopathic thrombocytopenia refractery to therapy of cyclosporine A in clinical practice - case report]. / Idiopatická trombocytopénia refraktérna na terapiu cyklosporínom A v klinickej praxi.

Primary immune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) is an autoimmune disorder characterized by isolated thrombocytopenia without abnormalities in the erythroid and myeloid/lymphoid lineages. The incidence of ITP in adults is estimated at approximately 1.6-3.9 per 100 000 persons/year. The aim of this study was to analyze a case report of a patient with diagnosed immune thrombocytopenia (D69.3) resistant to cyclosporine A therapy as well as an evaluation of factors that could contribute to an inadequate response to cyclosporine A. The results show a multifactorial origin of thrombocytopenia and a possible effect on refractivity to cyclosporine A therapy caused by long-term smoking, MDR-1 gene polymorphism, genetic predisposition to autoimmune diseases, allergic reactions as a manifestation of hypersensitivity in the immune system, controversial compliance of the patient, overcome infections as well as impact of drugs taken.Key words: immune thrombocytopenia refractery form cyclosporine A therapy platelets.

Identification of new phosphorylation sites of CD23 in B-cells of patients with chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common lymphoproliferative disorder in adults. Patients with B-CLL strongly express the CD23 - C type of lectin (low affinity IgE receptor, Fc epsilon RII), which is linked to B cell activation and proliferation. Phosphorylation in lymphocytes is tightly associated with regulation of protein activities, functional regulation and cell signaling, and may thus affect initiation and/or progression of the disease. Here we report changes in the phosphorylation of CD23 on threonine (pThr314) and two serine residues (pSer254, pSer265) in B lymphocytes of B-CLL patients, using a flow cytometry approach. The majority of tested patients with active forms of B-CLL presented a notable overexpression of CD23 along with pThr314, pSer254, and pSer265 CD23 phosphorylation positivity. Moreover, we have experimentally stimulated the CD23 phosphorylations in a subset of peripheral blood lymphocytes of healthy controls by phorbol-12-myristate-13-acetate treatment. This affects the activation of competent phosphorylation mediating kinases, resulting in the enhanced phosphorylation pattern. Together, these data confirm that CD23 protein is phosphorylated in B cells of B-CLL patients, report the identification of new CD23 phosphorylation sites, and suggest a possible role(s) of such phosphorylations in the activation of CD23 during the process of lymphocytic activation in B-CLL.