The role of ofatumumab in the treatment of B-cell lymphomas

Włączenie rytuksymabu do schematów chemioterapii przyniosło w ostatnich latach istotny postęp w leczeniu chłoniaków B-komórkowych, natomiast antygen CD20 pozostaje jednym z najatrakcyjniejszych celów terapeutycznych. Wciąż jednak nie wszystkich chorych z agresywnymi chłoniakami udaje się wyleczyć, a przewlekła białaczka limfocytowa pozostaje schorzeniem nieuleczalnym. Ostatnio opracowano przeciwciała monoklonalne anty-CD20 nowej generacji. Ofatumumab — w pełni ludzkie przeciwciało typu I skierowane przeciwko antygenowi CD20 — wiążące się z innym epitopem antygenu niż rytuksymab — w badaniach przedklinicznych charakteryzował się wyższą skutecznością w niszczeniu nowotworowych limfocytów B w mechanizmie cytotoksyczności zależnej od komplementu. W badaniach klinicznych I i II fazy przeciwciało to okazało się skuteczne w monoterapii oraz terapii skojarzonej przewlekłej białaczki limfocytowej oraz innych chłoniaków B-komórkowych, także u pacjentów opornych na rytuksymab. W ubiegłym roku ofatumumab zarejestrowano do leczenia przewlekłej białaczki limfocytowej opornej na fludarabinę i alemtuzumab. Ponadto trwają intensywne badania nad skutecznością tego leku w przypadku innych chłoniaków. W artykule przedstawiono mechanizm działania, skuteczność i bezpieczeństwo stosowania ofatumumabu na podstawie przeglądu aktualnych publikacji w B-komórkowych nowotworach układu chłonnego. Hematologia 2011, 2, 3: 246–255Integration of rituximab into chemoimmunotherapy regimens has recently brought significant progress in the treatment of B cell lymphomas, and the CD20 antigen remains one of the most attractive therapeutic targets. Despite of the recent progress in the field, not all patients with aggressive lymphomas can be cured, and chronic lymphocytic leukemia remains incurable disease. Recently, other anti-CD20 monoclonal antibodies have been developed. Ofatumumab — a novel, fully human type I anti-CD20 monoclonal antibody, that binds to an epitope different than rituximab, in preclinical studies showed higher efficacy in the destruction of neoplastic B cells in the mechanism of cytotoxicity depending on the complement. In early clinical trials, ofatumumab in monotherapy and in combination with other agents showed an activity against chronic lymphocytic leukemia and other B-cell malignancies, even in rituximab-resistant patients. Ofatumumab was recently approved for the treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia. This antibody is extensively tested for many other indications. The article presents the review of current publications concerning the mechanism of action, efficacy and safety of ofatumumab in a broad spectrum of B-cell neoplasms. Hematologia 2011, 2, 3: 246–25

Znaczenie oceny minimalnej choroby resztkowej u chorych na przewlekłą białaczkę limfocytową

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of mature B lymphocytes characterized by a heterogenous clinical course. Approximately 60% of cases require treatment initiation due to disease advancement. Immunochemotherapy enables achievement of durable remissions in some of the patients, however despite the observed complete responses relapses occur. These are explained by the persistence of residual leukemic cells in blood, bone marrow and lymph nodes, defined as minimal residual disease (MRD). Use of flow cytometry and molecular methods in assessment of treatment response allows for more detailed response quantification and detection of leukemic cells with ≥ 10-5 sensitivity. Elimination of MRD is an important prognosticator of durable remissions following immunochemotherapy. Furthermore, the significance of MRD assessment increases due to its possible role in CLL treatment individualization and potential surrogate marker of response without the need of long lasting observations. Herein in this publication, the clinical significance of MRD assessment emphasizing flow cytometric methodology is summarized.Przewlekła białaczka limfocytowa (CLL) jest chorobą limfoproliferacyjną o zróżnicowanym prze­biegu klinicznym wywodzącą się z dojrzałych limfocytów B. W około 60% przypadków ze wzglę­du na zaawansowanie choroby konieczne jest rozpoczęcie leczenia. Zastosowanie intensywnej immunochemioterapii pozwala uzyskać długotrwałe remisje u części pacjentów, niemniej mimo uzyskania całkowitych odpowiedzi dochodzi do wznowy choroby. Jej nawrót tłumaczy się obecnością rezydualnych komórek białaczkowych w szpiku kostnym, krwi obwodowej czy węzłach chłonnych, określanych mianem minimalnej choroby resztkowej (MRD). Zastosowanie cytometrii przepły­wowej (FLC) oraz metod molekularnych umożliwia wykrycie pozostałych komórek białaczkowych z czułością sięgającą co najmniej 10–5, co pozwala na dokładniejsze określenie odpowiedzi na lecze­nie. Eliminacja choroby resztkowej stanowi istotny czynnik rokowniczy długotrwałej odpowiedzi na immunochemioterapię. Ponadto znaczenie oceny MRD zwiększa się w związku z możliwością in­dywidualizacji leczenia CLL oraz oceny jego skuteczności bez konieczności długoletniej obserwacji chorych. W niniejszej pracy podsumowano znaczenie kliniczne oceny MRD w CLL ze szczególnym uwzględnieniem metodyki opartej na FLC

Firefighters’ knowledge of the knowledge of procedures for clearing the respiratory tract in an injured person with suspected infection with biological material (SARS-CoV-2) — a nationwide cross- -sectional study

Introduction: The aim of the study was to assess the knowledge of the procedure for clearing the respiratory tract and updated qualified first aid (QFA) 1a and 2a procedures by firefighters serving in State Fire Service (SFS) rescue and firefighting units, and their knowledge of the transmission of the SARS-CoV-2 virus. Material and methods: The cross-sectional study covered 19 408 firefighters (officers serving in SFS rescue and firefighting units from all over Poland). The study was conducted using the diagnostic survey method, the Computer Assisted Web Interview (CAWI) technique consisting of a set of particulars regarding a specific officer and the appropriate medical part of the survey. Results: In the group of 19,408 respondents, 99.31% were men (n = 19,275), while women accounted for 0.69% (n = 133; p < 0.001). The age of the respondents was in the range of 18–66 years, and the average age was 35.88 ± 7.14 years. The length of service was 11.95 ± 6.44 years. The knowledge of procedures 1a and 2a declared by the respondents [OR = 1.51 (95% CI: 1.22–1.86), x2 = 14.76], the ability to operate a suction unit [OR = 1.73 (95% CI: 1.44–2.08, x2 = 34.58)], the frequency of airway clearance training (p < < 0.001, x2 = 61.74). Only 15% of respondents used a suction unit on an injured person during operations. Conclusions: The knowledge of firefighters in the subject matter covered by the analysis is diverse, some firefighters have additional experience and practice from working in health care units. Professional development in the field of QFA supplemented with procedures 1a and 2a may translate into a lower risk of infection associated with airway clearing in the era of the pandemic. There is a visible need for constant training of SFS officers in terms of medical activities to maintain the knowledge of firefighters at a high initial level

Efficacy and safety of obinutuzumab-chlorambucil combination in the frontline treatment of elderly patients with chronic lymphocytic leukemia and comorbidities : real‑life data from Polish Adult Leukemia Group (PALG) analysis

Fludarabine- or bendamustine‑based upfront immunochemotherapy is the current standard of care in fit patients with chronic lymphocytic leukemia (CLL). These regimens are poorly tolerated by patients with comorbidities, for whom the obinutuzumab-chlorambucil combination became the recommended first‑line treatment. We aimed to analyze real‑life experience with the obinutuzumab-chlorambucil combination as the frontline treatment in elderly and unfit patients. The retrospective analysis included 86 elderly patients (median age, 74 years) with CLL and a significant burden of comorbidities, treated with obinutuzumab-chlorambucil as the frontline regimen. All patients had a Cumulative Illness Rating Scale score greater than 6 and/or creatinine clearance of 30 to 69 ml/min. Overall response rate at 2 months after treatment completion was 95.3%, with complete remission (CR) rate of 43% and partial remission (PR) rate of 52.3%. Stable disease rate was 4.7%. Progressive disease was not observed after treatment completion. The median progression‑free survival (PFS) was not reached after a median follow‑up of 18 months; estimated PFS at 30 months was 62%. We observed 6 relapses (7%), 3 (3.5%) in patients obtaining CR, and 3 (3.5%) in those with PR after immunochemotherapy. The most frequent adverse events were neutropenia and infusion‑related reactions (IRRs). Grade-3 neutropenia occurred in 11.6% of patients, and grade-3 IRRs, in 2.3%. There were no adverse events of grade 4 or 5. Our data confirm that the obinutuzumab-chlorambucil combination is an effective and well‑tolerated regimen in untreated CLL patients with comorbidities

The role of bendamustine in chronic lymphocytic leukemia with particular focus on the treatment of elderly patients

Przewlekła białaczka limfocytowa (CLL) jest najczęstszą postacią białaczki diagnozowanej u osób dorosłych. Wybór schematu leczenia oraz jego intensywność powinny być dostosowane indywidualnie do każdego chorego, z których większość ma ponad 65 lat i często wiele schorzeń współistniejących. Bendamustyna (BEN) jest odkrytym na nowo cytostatykiem łączącym właściwości fizykochemiczne oraz farmakologiczne leków alkilujących i analogów purynowych. W niniejszym artykule skoncentrowano się na omówieniu właściwości BEN, analizie skuteczności tego leku w CLL oraz ocenie profilu bezpieczeństwa substancji i miejsca w leczeniu chorych na CLL.Chronic lymphocytic leukemia (CLL) is the most common form of leukemia diagnosed in adults. Selecting the proper treatment regimen, and its intensity should be adjusted individually for each patient — most of them are over 65 years-old and have often multiple comorbidities. Bendamustine (BEN) is rediscovered cytotoxic agent combining physicochemical and pharmacological properties of alkylating agents and purine analogues. This article focuses on the presentation of the substance, the analysis of effectiveness of BEN in CLL and the assessment of the drug safety profile and its role in the treatment of patients with CLL

Retrospective analysis of nilotinib and dasatinib efficacy in second line treatment of chronic myeloid leukemia in Polish hematological centers

Until now, there has been no randomized study directly comparing the activity of second-generation BCR-ABL tyrosine kinase inhibitors (TKI-2G) nilotinib and dasatinib in chronic myeloid leukemia (CML). The aim of our study was to retrospectively analyze efficacy of nilotinib and dasatinib in the real life setting of CML with resistance or intolerance of imatinib. Of 108 included patients treated in polish hematology centers, 75 received dasatinib and 33 patients received nilotinib. Rates of complete cytogenetic response (CCyR) did not differ between the two groups of patients. After six months of therapy, CCyR was achieved in 34.7% of patients treated with dasatinib and 38.7% treated with nilotinib (p=0.86), while after 12 months, the CCyR rates were 60.0% and 77.0% in dasatinib and nilotinib groups, respectively (p=0.11). Moreover, we have not observed any significant difference in the probability of progression-free survival (p=0.89) or overall survival (p=0.99) between patients treated with these two TKI-2G. In conclusion, the results of our analysis indicate that nilotinib and dasatinib have comparable and satisfactory efficacy in the treatment of CML patients refractory or intolerant to imatinib. Our findings support current strategy of choice of IKT-2G according to drug toxicity profile and risk of specific adverse events in an individual patient