The identification of independent prognostic factors for elderly patients with relapsed and/or refractory multiple myeloma

Introduction: Multiple myeloma (MM) is a malignant plasma cell disorder. It is regarded as an incurable disease with typical complications which in particular are anemia, kidney failure and congestive heart failure (CHF). Cardiac natriuretic peptides BNP and NT-proBNP can be used to screen for left ventricular systolic dysfunction in patients with symptoms suggestive of heart failure. The aim of the present study was to examine if the levels of BNP and NT-pro-BNP predicts mortality in patients with MM and concomitant CHF. Material and method: The study population included 45 (m -16, f-30) adult patients (pts) with refractory or relapsed/refractory MM. The subjects satisfy the following criteria to be enrolled in this study: (1) availability of proven CHF with New York Heart Association (NYHA) grades I-III; (2) must be documented diagnosis of MM and estimated about its chemotherapy; (3) the presence of anemia with Hb less than 8.0 mg /dL (4) ECOG performance status score not more than 2; (5) basic therapy for CHF (inhibitor APF ± diuretic) was spent not less than within last 2 weeks. Ihe study did not include pts with NYHA grade IV, the constant form of atrial fibrillation, heart diseases and/or a heavy arterial pathology. For the treatment of MM 28 (62 %) pts have received “salvage” chemotherapy with bortezomib, 15 (33 %) - alkylate drug therapy and 2 (5 %) - high doses of dexamethasone. Levels of NT-proBNP and a BNP-fragment in blood serum have been defined by ELIZA at the moment of enrolling in the study. ROC-curves were used to calculate the threshold concentrations of BNP and NT-proBNP. Overall survival (OS) was estimated using Kaplan-Mayer method. Results and discussion: The age median of patients at the enrollment was 66 (range 42-83) years. 3 (7 %) pts had IIA stage on Salmon-Durie, 22 (49 %) - IIIA and 20 (44 %) - IIIB. 33 (73 %) pts had evidence of CFH grade I, 9 (20 %) - II and 3 (7 %) - III. An objective response on MM treatment was reached 26 (58 %) pts, including complete response (CR) and very good partial response (VGPR) -7 (1 6 %) pts. 33 (73 %) pts were alive with a median follow 11 months. The predictive values of BNP-fragment levels on OS were not detected. Analysis of the activity of NT-proBNP allows detecting of a significant correlation with grades of CFH and OS (p < 0.05). The levels of NT-proBNP more than 0.93 ng/ml (sensitivity 82%, specificity 62%) was identified as a predictor of the likely risk of mortality. 1-year OS of pts with proBNP levels in the blood above 0.93 was 53% versus 78% (p < 0.05) for subjects with a lower level of this peptide. Conclusion: NT-proBNP levels in blood serum > 0.93 ng/ml were identified as the adverse factor for patients with MM and concomitant CHF. BNP-fragment levels in this clinical situation have not predictive value

Pomalidomide for the management of relapsed and refractory multiple myeloma: a case report and review of literature

Relapsed and refractory multiple myeloma (MM) is defined as progression during anticancer therapy, or within 60 days of therapy completion. Patients with double resistance to bortezomib and lenalidomide that is two key anti-myeloma drugs are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is an immunomodulatory drug third generation, studied in combination with low-dose dexamethasone (LDD) as salvage therapy for patients with double refractory. This article reviews the clinical pharmacology, therapeutic efficacy and safety, dosage and administration, peculiar properties of the practical application of pomalidomide. The article is illustrated by the description of a 59-year-old woman with relapsed and refractory MM, who received pomalidomide in combination with LDD. Medical history prior to treatment with pomalidomide was included 8 lines of therapy conducted over 6.5 years, with the formation of the double refractory to lenalidomide and bortezomib. In March 2012, treatment with pomalidomide (4 mg days 1–21 of a 28-day cycle) and LDD (160 mg / cycle) has been started as the ninth line. In total, up to March 2014 the patient received 30 cycles of therapy with pomalidomide. After the first 2 cycles documented partial response (52 % reduction of IgGk), the deepest response is received after 10 cycles (82 % reduction). The patient is alive at the time of this article. The duration of response to pomalidomide is 25 months and overall survival from the time of his appointment is more than 37 months. In addition, this review presents the results of base clinical trials testing pomalidomide and LDD. Problems of development of new treatment regimens based on pomalidomide for relapsed and refractory MM are also discussed

Long-term continuous treatment as a new strategy for relapsed or refractory multiple myeloma

The prognosis for patients with multiple myeloma has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens, and improved management of toxicities. Treatment of relapsed or refractory multiple myeloma represents a vital aspect of the overall care for patients with multiple myeloma and a critical area of ongoing biologic and clinical research. The choice of regimen at relapse is usually based on the prior response, toxicities, assessment of prognostic factors, age and comorbidities of individual patients, their somatic condition and expected effectiveness and tolerability. The new drugs, such as ixazomib, carfilzomib, pomalidomide, daratumumab and elotuzumab in combinations in doublet or triplet regimens, have greatly increased the treatment armory against myeloma. Long-term continuous therapies as a new strategy for relapsed or refractory multiple myeloma have been shown to provide an eradicating of minimal residual disease and deep prolong responses, with the goal of improving progression-free survival and overall survival. The integration of novel agents into the treatment paradigm has shifted the perception of multiple myeloma from an incurable fatal disease to a manageable chronic one. This review discusses the most recent and effective regimens for the relapsed or refractory multiple myeloma treatment, based on the results of recently published phase II and III clinical trials. Analyses the current clinical trial data discussed with a focus on lenalidomide or bortezomib as a basis of new treatment regimens

Ixazomib in the treatment of relapsed multiple myeloma

Ixazomib (NINLARO, Takeda Pharmaceutical Company Limited) is the first oral proteasome inhibitor which approved in combination with lenalidomide and dexamethasone (IRd) for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is a boron-containing selective and reversible proteasome inhibitor that have high antitumor activity with excellent safety. This combination was approved based on the results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival (PFS) for IRd versus placebo-Rd: median: 20.6 vs 14.7 months; hazard ratio (HR): 0.74, P = 0.012. PFS was improved in both high-and standard-risk cytogenetics subgroups with median PFS in high-risk patients 21.4 vs 9.7 months (HR 0.54; P = 0.021) and in standard-risk patients 20.6 vs15.6 months (HR 0.64; P = 0.007). The addition of ixazomib to Rd regimen was associated with minimal additional toxicity. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. No significant inhibition of neuronal cell survival protease HtrA2/Omi was noted in response on ixazomib treatment in vitro that explains its minimal clinical peripheral neuropathy. The present review addresses the current knowledge regarding the clinical use of ixazomib in relapsed myeloma patient and the prospects for further expansion of therapeutic indications

Management of immune thrombocytopenia during COVID-19 pandemic

Introduction . The COVID-19 pandemic has challenged health professionals and patients suffering from haematological diseases with embarrassed diagnosis, treatment, surveillance, social distancing and other constraints. Aim  — addressing therapy for immune thrombocytopenia (ITP) during the COVID-19 pandemic in the light of own experience, as well as national and international professional medical community guidelines. Main findings . A standard choice in COVID-19-negative ITP patients are conventional, e.g., glucocorticosteroid (GCS) and intravenous immunoglobulin therapies. An early transfer to thrombopoietin receptor agonists (rTPO) appears optimal as reducing the infection risk in GCS withdrawal and significantly improving the stable remission rate without supportive treatment. Combined ITP–COVID-19 patients should consider a prednisolone treatment of 20 mg/day, provided an absent active bleeding. The dose may increase to 1 mg/kg/day in no response after 3–5 days. ITP patients admitted for COVID-19 should start weight‐based LMWH thromboprophylaxis upon attaining a platelet count of ≥ 30 × 109 /L. Chronic ITP patients should carry on usual treatment with standard SARS-CoV-2 preventive and social distancing measures. We exemplify three contrasting clinical cases of COVID-19-comorbid thrombocytopenia and discuss the ITP differential diagnosis and therapy. Two patients received GCSs and rTPO agonists (romiplostim, eltrombopag), while GCSs alone provided for platelet response in the third case. All patients showed a good clinical and biological response. Issues in SARS-CoV-2 vaccination are discussed

Myelodysplastic syndromes: therapeutic problems and decisions (review)

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA) and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q) the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine) are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.</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

Myelodysplastic syndromes: therapeutic problems and decisions (review)

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA) and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q) the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine) are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review

EPIDEMIOLOGY OF MULTIPLE MYELOMA ACCORDING TO THE КIROV REGION POPULATION REGISTERS

The aim of this study was to analyze the basic epidemiological parameters of MM in the Kirov region based on own regional population register data.Materials and methods. Five hundred and sixty-seven patients with newly diagnosed MM between 1994 and 2016 were included. The median age was 64 years (range, 29–90).  The age-standardized incidence of MM in Kirov region was 1.8 cases per 100.000/year.Results. During research period (23 years) we have the positive trend of the incidence and prevalence of MM and negative tendency of mortality every year. Our prognosis of the intensive incidence in Kirov region is 2.2–2.3  cases per 100.000 in 2017–2019  years. The 5-year overall survival rate (5y-OS) was 18 % (1994–1999);  24 % (2000–2005) and 36 % (2006–2011) respectively. The median OS was 28; 26 and 38 month respectively. The median OS for patients who diagnosed in the period 2012–2016  was not achieved. The reason for the increase in the prevalence of the disease and the reduction in mortality is the greater effectiveness of new bortezomib-containing chemotherapy regimens.Conclusion.  Аmong the Kirov region population standardized incidence of MM  is 1.8 cases per 100.000/year.  The  prevalence of MM in the Kirov region has a linear growth trend from 3 to 11 patients per 100.000 peoples within the analyzed period of observation 1994–2016. OS increased from 18 to 36 % in the period from 1994 to 2011. OS of MM patients has been increasing since 2006, due to using bortezomib-containing treatment options and autologous stem cell transplantation. In general, the 5-year OS increased from 18 to 36% in the period from 1994 to 2011

Combination of bendamustine and rituximab in the management of relapsed and refractory chronic lymphocytic leukemia: the results of retrospective study

Efficacy and safety results of rituximab and bendamustine combination (Scheme BR) in patients with relapsed and refractory chronic lymphocytic leukemia (CLL) are presented. From 01.2012 to 04.2013, the treatment was initiated in 43 patients (21 with relapses are sensitive to the last line of therapy; 22 – with refractory CLL). Median age at start of therapy was 63.5 years (range from 43 to 81 years). In 40 patients response was evaluated according to NCI-WG criteria (1996). Complete remission (CR) is documented in 5 (12.5 %) cases, partial (PR) or nodular partial remission (nPR) in 17 (42.5 %) cases. MRD-negative CR was achieved in 1 (20.0 %) of 5 patients with CR. With 23.5 months of median follow-up for surviving patients 2-year progression-free survival (PFS) was 47.2 ± 8.5 % (median – 18.5 months), overall survival (OS) – 66.9 ± 7.9 % (median not achieved). Hematological toxicity Grade 3–4 occurred in 15 (34.9 %) cases, same degree infectious complicationsin 5 (11.6 %) cases. Patients received 3 or more therapy lines before this treatment (37.5 ± 16.1 % against 74.7 ± 8.3 %; p = 0.016), with «bulky disease» more than 10 cm (0.0 % vs. 75.4 ± 7.5 %; p &lt; 0.001) and received rituximab in combination with chemotherapy in the previous lines, compared to the «naive» cases (44.1 ± 10.5 % against 92.9 ± 6.9 %; p = 0.009) have significantly worsened 2-year OS