[Multiple myeloma: response to treatment and survival of patients according to the interim analysis of the Russian observational, retrospective-prospective, multicenter cohort study (MULTISPECT)].

AIM: The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. MATERIALS AND METHODS: The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. RESULTS: The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. CONCLUSION: The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.

[Gene expression of vascular endothelial growth factors and their receptors in different variants of the course of multiple myeloma].

AIM: To determine the significance of the angiogenic activity estimated from the gene expression of the vascular endothelial growth factors (VEGFs) VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR1, VEGFRls, VEGFR2, and VEGFR3 in the mononuclear cell fraction of bone marrow (BM) aspirates with tumor plasma cells predominating in different variants of the course of multiple myeloma (MM). MATERIALS AND METHODS: The gene expression of VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFRI, VEGFRls, VEGFR2, and VEGFR3 was determined by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: VEGF-A, VEGF-C, VEGF-D, as well as VEGFR1, VEGFRls, VEGFR2, and VEGFR3 were expressed showing different intensities in the mononuclear cell fraction of BM aspirates with a predominance of tumor plasma cells in the patients with MM, which allowed patient groups to be identified. In the group of high gene expression of VEGFs and their receptors, the number of clusters of plasma cells and vascular endothelium in the BM aspirates and the degree of osteolysis in the skeletal bones of patients with MM were significantly higher than those in the group of low or absent gene expression. The survival in the latter group was significantly higher. CONCLUSION: The investigation could provide an estimate of angiogenic processes in MM and establish their association with clinical manifestations and cytological characteristics.

[Effectiveness of bortezomib and bortezomib-containing programs for the treatment of recurrent and resistant multiple myeloma].

AIM: To evaluate the effectiveness of bortezomib and bortezomib-containing treatment programs in the therapy of resistant and recurrent multiple myeloma (MM) within a large unicenter study in real clinical practice conditions. SUBJECTS AND METHODS: The study enrolled 101 patients (48 men and 53 women aged 34 to 77 years, mean age 54 years) with resistant and recurrent MM. According to the types of paraprotein (PIg), the authors revealed the usual distribution: G, 60.7%; A, 23.8%; BJ, 13%; M, 1.15%; D, 1.15%. The PIg kappa/lambda light chain ratio was 1.7. The complicated course of the disease was noted in 50.4% of the patients. The patients were randomized into 4 treatment groups: V1--velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11 of a 21-day cycle; V2--velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, melphalan 20 mg orally on day 2 of a 28-day cycle; V3--velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, melphalan 9 mg/m2 orally for 4 days, prednisolone 60 mg/m2 orally for 4 days of a 42-day cycle; V4--velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, melphalan 9 mg/m2 orally for 4 days, prednisolone 60 mg/m2 orally for 4 days, cyclophosphanum, 250 mg/m2 intravenously dropwise on days 1 to 7 of a 60-day cycle. An average of 6.5 induction treatment cycles was performed. RESULTS: Amongst the 27 patients receiving bortezomib therapy (V1), an objective response to therapy was obtained in 70.3%, including a complete response (CR) in 18.5%, a near-complete response (NCR) in 14.8%, and a partial response (PR) in 37%. When a combination of melphalan and bortezomib (VM; V2) was used, 22 patients achieved CR, NCR, and PR, which were equal to 9, 13, and 45.4%, respectively. In the group of 20 patients on the triple combination (VMP; V3), the amount of CR and PR was 90%. The use of the quadruple combination regimen (V4; VMCP) yielded an objective response (CR + NCR + PR) in 63.2% of the 32 patients, which did not virtually differ from other programs other than V3. However, the amount of CR +NCR (43.6%) was more than that in other groups. When all these programs were implemented, clinically significant myelotoxicity and grades 3 and 4 polyneuropathy were not seen. When the bortezomib-containing programs were applied, the median overall survival from the moment of diagnosis was 103 months. CONCLUSION: Bortezomib in the monotherapy and multidrug therapy for resistant and recurrent MM shows immediate and long-term benefits and a low toxicity.

[Pharmacodynamic characteristics of velcade efficacy in resistant and recurrent multiple myeloma: determination of free light chains of blood serum immunoglobulins].

AIM: To ascertain individual sensitivity to velkeid in patients with resistant and recurrent multiple myeloma (MM) by determination of free light chains (FLC) of serum immunoglobulins. MATERIAL AND METHODS: Fourteen patients with MM stage III (Gcappa-5, Glambda-2, Acappa-3, Alambda-1, BJcappa-3) aged 52-75 years with documented resistance to treatment or recurrence received second-line monotherapy with velkeid. The drug was injected intravenously (jet) in a dose 1.3 mg/m2 on the treatment day 1, 4, 8 and 11. Free light chains concentration was examined with antibodies to their latent determinants (Binding Site, UK) on nephelometer (Hitathi-911, Japan) on velkeid treatment day 1, 2, 3, 5, 9 and 12. RESULTS: Nine patients showed lowering of FLC concentration and responded to treatment by Durie criteria. CONCLUSION: Dynamic follow-up of FLC concentration of the tumor clone in resistant and recurrent MM evaluates pharmacodynamics of the drug. The method provides prognosis of late clinical results.

[Clinical characteristics of velcade cumulative effect in resistant and recurrent multiple myeloma].

AIM: To assess efficacy of velcade monotherapy in patients with resistent and recurrent multiple myeloma (MM). MATERIAL AND METHODS: Velcade was given to 29 patients (11 males and 18 females at the age 41-73 years) with resistant and recurrent MM of stage 3. A standard scheme was used - 1.3 mg/m2 iv jet on day 1, 4, 8 and 11. The cycle was 21 days, a total of 6 cycles. All the patients were examined immunochemically for serum and urine PIg. An antitumor effect was studied. RESULTS: After, on the average, 3 courses of velcade therapy PIg reduction was 31.3%. The response was complete (CR) in 3.4%, partial (PR) in 44.6%, minor response (MR) in 17% and no response (NR) in 35% patients. After 6 cycles of velcade monotherapy given to 23 patients PIg reduction was 59%. CR, PR, MR, NR were seen in 2 (8.7%), 11 (47.8%), 4 (17.4%), 6(26.1%) patients, respectively. Progression occurred in 8.7%. After 3 cycles of velcade therapy in 29 patients an objective response occurred in 48%, after 6 cycles it increased to 56.5%. The group with poor respose (MR+NR) reduced from 52 (after 3 cycles) to 43.5% (after 6 cycles) patients. Cumulative toxicity of velcade 10 days after the end of cycles 3 and 6 was absent.

[Linear and adhesive phenotype of tumor lymphocytes and clinical course of chronic leucosis].

Determination of chronic lymphatic leukemia immunological phenotype, performed by the authors, was based upon the study of quantitative expression of membrane differentiation antigens on peripheral blood lymphocytes. The research included study of co-expression of adhesion molecules, belonging to the following families: beta 2 integrins (CD 11 beta, CD 18), immunoglobulins (CD 50), and CD 38 on tumor blood B-lymphocytes of various CD-types and T-lymphocytes in chronic leucosis. The authors developed a functional model of trans-endothelial migration of peripheral blood lymphocytes in chronic chronic lymphatic leukemia, taking into account their membrane adhesive characteristics and serum level of CD 50. The researchers determined clinical importance of the expression of linear and adhesive antigens on peripheral blood lymphocytes, and soluble HLA-1 (sHLA-1) serum levels in patients with chronic lymphatic leukemia.

[The extratumor mechanisms of osteolysis in multiple myeloma and the means for their correction]. / Vneopukholevye mekhanizmy osteoliza pri mnozhestvennoi mielome i puti ikh korrektsii.

In 70 patients with stage III multiple myeloma (MM) the authors studied spontaneous and lipopolysaccharide-induced production of interleukin-1 (IL-1) and interleukin-6 (IL-6) by blood and bone marrow mononuclear cells, concentration of parathyroid hormone and vitamin D3 in the serum. Bone marrow density was measured at photon absorption (Gambro), in patients treated with osteoprotectors bonefos and oxidevit before and after therapy (3.5-6 month course). It is shown that in MM there is a pathogenetic association between production of osteotropic IL-1, IL-6 and bone demineralization. The cases with reduced concentration of Ca and P ions in the serum (4 and 5.7% of patients, respectively) and increased PTH concentration (7%) suggest the existence of new, extratumor mechanisms of osteolysis. It is found that biphosphonates are optimal osteoprotectors. Bonefos (chlodronat, Lieras, Finland) arrests osteolysis proved by a significant increase of bone marrow density and clinical effect.