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Aim: To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH)., Materials and Methods: Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (1:1) into 2 treatment groups: investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve LDH concentrationtime (AUCLDH) throughout the study period weeks 527., Results: The difference between the mean AUCLDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/ldays. The 95% CI limits for the difference in mean AUCLDH values between the groups fit the preset 95% CI [-146 500.9146 500.9] U/ldays and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups., Conclusion: The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration-time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration-time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056., (© 2021. The Author(s).)

Aim: To study the experience in managing patients with acute promyelocytic leukemia (APL) diagnosed in different periods of pregnancy., Subjects and Methods: Nine women with APL were treated in 1998-2013. When APL was diagnosed in the first trimester of pregnancy, the latter was terminated (n = 1); when its diagnosis was made in the second trimester, chemotherapy (CT) followed by delivery (D) was performed (n = 3); when it was done in the third trimester, D followed by CT was done in relation to gestational age (n = 2) or these were performed at a later gestational age (n = 1). APL was treated in 5 and 1 patients according to the AIDA protocol and the 7+3 plus ATRA one, respectively., Results: All the patients with APL achieved remission after the first cycle of induction CT; 5 of the 6 patients did at the moment of delivery; one patient underwent emergency delivery during cytopenia after the cycle. The gestational age at delivery after CT was 34 (34-40) weeks. Spontaneous term labor occurred in 2 patients at an obstetric hospital. Cesarean section was made in 4 of the 6 patients. All babies were born alive, healthy, and without developmental abnormalities. Their age at the time of analyzing the results was 2.5 months to 15 years. Four of the 9 patients are presently alive. Late recurrences occurred in 3 (33%) patients. The median overall survival is 26 (0.25-128) months; the median relapse-free survival is 17.5 (0-127) months., Conclusion: APL treatment in pregnant women, which is aimed at saving two lives, is effective and reasonable.

Aim: To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009., Materials and Methods: The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients., Results: The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30 10(9)(/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses). CONCLUSION; The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.

Aim: Systematization of the results of 20-year multicenter randomized trial of the efficacy of treatment of acute myeloid leukemia (AML) of adults; presentation of the design of the study of the strategy of consolidation and maintenance therapy after high-dose consolidation initiated in 2007., Material and Methods: Treatment outcomes on the protocol AML-01.01 are presented for 354 AML patients from 29 hematological centers located in 22 towns of Russia and 2 towns of Ukraine. The patients were randomized into 3 groups by variant of therapy: 124 patients (62 males and 62 females; age median 42 years) received 4 courses of 7+3+VP-16 and 5 courses of maintenance therapy (7+3 with thioguanin); 130 patients (65 males and 65 females, age median 41 year) received 2 courses of 7+3+VP-16, 2 courses 7+3, maintenance--5 courses 7+3 with thioguanin; 126 patients (57 males and 68 females, age median 40 years) were given 2 courses of 7+3+VP-16, 2 HAD courses, treatment discontinuation., Results: A complete remission after the first course of 7+3+VP-16 was achieved in 55% patients, after the second course--in 30% after the course 7+3+VP-16 or 7+3 with mitoxantron, in 70%--after NAM. Overall and recurrence-free survival were 18 and 35%; 30 and 20%; 36 and 30%, respectively. There was no significant difference in efficacy of the treatment scheme., Conclusion: The multivariate analysis has shown that a leading factor having impact on treatment results was the number of randomized patients: the less patients were randomized, the worse were the results.

Altogether 21 patients were examined for an erythropoiesis inhibitor contained by the IgG fraction of the blood plasma. All these patients suffered from hemopoiesis depression. The inhibitor identified in the immunoglobulin fraction of the blood plasma of 40% of the patients manifested itself at the stage of erythroid precursors of bone marrow cells. The role of the humoral inhibitor in the development of erythropoietic disorders in these patients is under discussion.