Solitary (extramedullary) plasmocytoma. Clinical recommendations

Solitary (extramedullary) plasmocytoma. Clinical recommendation

ELEVATE-TN Study. New data of acalabrutinib in first-line treatment of chronic lymphocytic leukemia. Resolution

Over the past decade, we have seen a significant change in modern approaches in the first-line treatment of chronic lymphocytic leukemia (CLL). The CLL-10 study data established the FCR regimen as the treatment of choice for younger patients with limited comorbidities, while for patients older than 65 years, the BR regimen is more often considered as less toxic one. According to published data, 46% of patients with newly diagnosed CLL have comorbidities. Moreover, high-risk patients with del(17p) and/or TP53 mutation do not have response on immunochemotherapy (ICT) most often. Thus, about 1/2 of the patients cannot be treated or will not respond to standard ICT regimens. Targeted therapy with Brutons tyrosine kinase (BTK) inhibitors is an important option of the first-line treatment of patients with CLL. Acalabrutinib is a highly selective second-generation BTK inhibitor that does not inhibit EGFR, ITK or TEC targets. Acalabrutinib in combination with obinutuzumab or as monotherapy can be considered as a highly effective and safe option of the first line of CLL therapy. Based on the hight selectivity of the agent, acalabrutinib can be considered as the preferable option for patients who are not eligible for ICT, including patients with commodities, such as cardiovascular diseases or risk factors for their development

Daratumumab Monotherapy for Relapsed or Refractory Multiple Myeloma: Results of an Early Access Treatment Protocol in Europe and Russia

Introduction Daratumumab is a human IgGκ monoclonal antibody targeting CD38. Despite the demonstrated benefit of daratumumab in multiple myeloma, not all patients have access to commercially available daratumumab. Here we report a pooled analysis of patients from the UK, Spain, Italy, and Russia enrolled in an open-label, early access treatment protocol (EAP) that provided daratumumab (16 mg/kg) monotherapy to patients with heavily pre-treated relapsed or refractory multiple myeloma (RRMM). Methods Intravenous daratumumab 16 mg/kg was administered to patients who had received ≥ 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and an IMiD. Safety and patient-reported outcomes data were collected. Results A total of 293 patients received  ≥ 1 dose of daratumumab. The median duration of daratumumab exposure was 4.2 (range 0.03–24.1) months, with a median number of 13 (range 1–37) infusions. The overall response rate was 33.1%, and the median progression-free survival was 4.63 months. Grade 3/4 treatment-emergent adverse events occurred in 60.1% of patients, of which the most common were thrombocytopenia (18.8%), anemia (11.9%), and neutropenia (11.6%). The most common serious adverse events were pneumonia (4.4%) and pyrexia (4.1%). Infusion-related reactions occurred in 45.1% of patients. The median change from baseline in all domains of patient-reported outcome instruments (European Quality of Life Five Dimensions Questionnaire [EQ-5D–5L], European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ-C30], and EORTC Multiple Myeloma Module [QLQ-MY20]) was generally 0 or close to 0. Conclusion These EAP results are consistent with those from previous trials of daratumumab monotherapy and confirm its safety in patients from Europe and Russia with heavily pre-treated RRMM. Trial Registration ClinicalTrials.gov identifier, NCT02477891

ОТЕЧЕСТВЕННЫЙ ОПЫТ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ПРОЯВЛЕНИЙ КОЖНОЙ ТОКСИЧНОСТИ У ПАЦИЕНТОВ МКРР, ПОЛУЧАЮЩИХ ИНГИБИТОРЫ EGFR, НА ПРИМЕРЕ ПРЕПАРАТА ПАНИТУМУМАБ

The results of the first national experience of skin toxicity correction in patients with metastatic colorectal cancer (mCRC) receiving EGRF-inhibitors shown on the example of using of Panitumumab. The collection and evaluation of the data were produced in the framework of the project of the working group on maintenance therapy of Russian society of clinical oncologists and chemotherapeutists (RUSSCO) to develop recommendations for the prevention and treatment of dermatological toxicity in patients receiving EGFR-inhibitors. The project involved 10 centers in Russia.  In 58 patients receiving Panitumumab, the efficacy of prophylactic medication and symptomatic treatment of clinical manifestations of dermatological toxicity using available remedies was evaluated. The results confirm the effectiveness of preventive therapy. Optimal correction schemes of various manifestations of dermal toxicity were developed depending on the clinical manifestations and severity.Освещены результаты первого отечественного опыта коррекции кожной токсичности у пациентов мКРР, получающих ингибиторы EGRF, на примере препарата Панитумумаб. Сбор и оценка данных произведены в рамках проекта рабочей группы по поддерживающей терапии Профессионального Общества онкологов-химиотерапевтов (RUSSCO) по разработке рекомендаций для профилактики и лечения дерматологической токсичности у пациентов, получающих ингибиторы EGFR. В проекте принимали участие 10 центров РФ. У 58 пациентов, получавших Панитумумаб, оценивалась эффективность профилактической медикаментозной и симптоматической терапии клинических проявлений дерматологической токсичности доступными средствами. Полученные результаты подтверждают эффективность профилактической терапии. Разработаны оптимальные схемы коррекции различных проявлений кожной токсичности в зависимости от клинических проявлений и степени тяжести

PREVENTION OF THROMBOTHIC COMPLICATIONS IN CANCER PATIENTS IN HIGH-RISK GROUPS

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Cancer-associated thrombosis is a major cause of morbidity and mortality in patients with cancer. Several risk factors for developing venous thrombosis usually coexist in cancer patients including surgery, hospital admissions and immobilization, the presence of an indwelling central catheter, chemotherapy. Effective prophylaxis and treatment of VTE reduced morbidity and mortality, and improved quality of life. Low-molecular-weight heparin (LMWH) is preferred as an effective and safe means for prophylaxis and treatment of VTE

Modern concepts of biosimilars in hematology and oncology

Biologics are large protein or polypeptide molecules produced by living organisms, which largely determine the efficiency of modern anticancertherapy. Biological products that destroy cancer cells and protect normal patient tissue led to progress in the treatment of breast cancer, colon cancer, kidney cancer, malignant lymphomas and other diseases. But the high cost and complexity of production limit their use. The expiration of patent protection for a number of biological products resulting to the possibility of reduces their costs when issuing an alternative manufacturer. At the same time, biosimilars are produced by living cells (as the original protein molecules), which led to serious difficulties in reaching their identity. The European Union has developed special registration rules for these preparations in order to avoid lack of efficacy or increased toxicity. They include regulations to determine the quality of biological products, requirements for pre-clinical and clinical studies, according to its specific characteristics, as well as the requirements for pharmacovigilance. Implementation of such a strategy has to register in the EU several biosimilars of granulocyte colonytimulating factor. For one of them – Zarzio – in several clinical studies fully comparable efficacy and tolerability with the original preparation was shown, thus providing a significant reduction of treatment cost with equal efficacy and toxicity.</p

Role of biosimilars in neutropenia prevention in cancer patients

Decreasing the neutrophils count in peripheral blood after intensive chemotherapy (CT) dramatically increases the risk of infectious complications.As a consequence, treatment costs significantly increased and patients quality of life reduced. Correction of neutropenia is possible with granulocyte colony stimulating factor (G-CSF) – a human protein produced by recombinant technology and is able to support the survival and proliferation of hematopoietic stem cells. Pharmacoeconomic studies have shown that G-CSF reduces the frequency of hospitalization and antibiotics using, which can reduce the treatment cost. The use of G-CSF allows to reduce early and infection mortality after chemotherapy, providing background to prolonging life especially for the elderly (over 65 years) and debilitated patients. The drug is included in all international recommendations. However, its use in Russia is limited due to high cost.Part of the policy aimed to reducing protein drugs cost and increase their availability is the creation of biosimilars protein drugs with proven effective. At the same time biosimilars as the original protein molecules are living cells products, causing serious difficulties in achieving their identity. To eliminate the risk of reducing the effectiveness or increase the toxicity, the European Union established regulations for the determination the bioproducts quality, a detailed description of the requirements for pre-clinical and clinical research, as well as the requirements for pharmacovigilance. Registered in the EEC countries G-CSF biosimilars have been first studied in healthy volunteers, and then in controlled clinical trials in comparison with the reference drug. High efficacy of one such G-CSF biosimilars (Zarsio®) was shown in controlled clinical trials of 170 patients with breast cancer receiving intensive chemotherapy with Docetaxel and Doxorubicin. Total in the study only 6 % cases of febrile neutropenia (FN) was registered – all within the first chemotherapy cycle. Hospitalization due to FN was required in 3.5 % of patients, and none of these patients did require therapy in the Intensive Care Unit (ICU). Intravenous antibiotics received only 5.3 % of patients with FN. The average duration of severe neutropenia in first cycle in patients treated Zarsio® was 1.8 days compared with 7 days in the control group without the growth factors support. Expected side effects (musculoskeletal pain, leukocytosis, thrombocytopenia, and headache) were of equal frequency in Zarsio® and Neypogen® groups. Serious adverse events were not observed, as well as deaths in all studies. Since 2009, the drug has been successfully used in oncology and hematology patients, which allowed within the expanded pharmacovigilance conduct a retrospective analysis of the effectiveness of neutropenia prevention after the change from the reference preparation filgrastim (GCSF) – Neypogen® on G-CSF biosimilars Zarsio® in general oncology practice which showed comparable results at a lower treatment cost</p

Influence of low molecular weight heparin on cancer patients’ survival

There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis). Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH) over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa) have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa).Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042).</p

Anemia in cancer patients: current treatment options (review)

The review presented the causes and pathogenesis of anemia in cancer patients. Also anemia negative impact on patients’ quality of life and chemotherapy efficacy and current clinical treatment recommendations with use of erythropoiesis stimulating agents and iron supplements are discussed. Special attention is paid on the effectiveness of modern intravenous iron preparation.</p

Approaches to improvement of treatment results of malignant tumors in adolescents and young adults

<p>This article provides an overview of clinical and biological features of most common malignant tumors in adolescents and young adults. The most effective pediatric and oncological treatment approaches to described diseases based on own experience are summarized.</p