multiple myeloma

Management of relapsed and refractory multiple myeloma: literature review and our data. Part III

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

Abstract

Advances in treatment options for patients with multiple myeloma have made a significant impact on overall survival and have helped to achieve the rates of response and duration of remission previously not unachievable with standard chemotherapy-based approaches. These improvements are due, in a large part, to the development of the novel agents, including bortezomib, thalidomide, and lenalidomide, each of which has substantial single-agent activity. Combinations of bortezomib, thalidomide, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. However, when patients are unresponsive to immunomodulatory drugs and bortezomib, the prognosis becomes poor. A number of novel agents are being tested in multiple myeloma, but relapsed/refractory multiple myeloma still represents a challenge and difficult area for drug development. Therefore, the new agents are needed. In addition, a large number of second- or third-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. Such agents as carfilzomib, pomalidomide, vorinostat, panobinistat, romidepsin, perifosine, tanespimycin, bendamustine, and elotuzumab are just a few out of many exciting new compounds that are being tested in phases I, II, or III of clinical trials for relapsed patients. This review covers the new strategies, based on clinical trials and our own data and intended for optimizing treatment outcomes in relapsed/refractory multiple myeloma. We describe the various classes of novel drugs under investigation and discuss the pros and cons of the data obtained in preclinical and clinical studies. The adverse effects of the new drugs are presented in detail.

Keywords: multiple myeloma, relapsed/refractory multiple myeloma, bortezomib, thalidomide, lenalidomide, carfilzomib, pomalidomide, treatment, complete remission, overall survival, neuropathy.

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Multiple myeloma (management of newly diagnosed patients): literature review and our on data. Part II

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

ABSTRACT

Over the last decades, survival rates for young patients with multiple myeloma markedly increased mainly due to the use of autologous stem cell transplantation (ASCT) and new highly efficacious rescue therapies. In patients with multiple myeloma over 65 years of age, a combination of melphalan and prednisone (MP) is traditionally used. Introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors substantially changed the therapeutic approach to the disease. Many double-, triple-, and quadruple-agent combinations were studied in the patients with newly diagnosed multiple myeloma. It was established that the achievement of complete response (CR) is an independent predictor of prolonged progression-free survival (PFS) and overall survival (OS). The data from prospective trials completed suggest that the best available strategy to achieve high CR rates and prolong its duration includes an induction therapy with a triple-agent bortezomib- or IMiDs-based regimen followed by ASCT and consolidation/maintenance with IMiDs or proteasome inhibitors. The vast majority of elderly patients with MM are ineligible for ASCT. Introduction of novel agents such as thalidomide, bortezomib, or lenalidomide considerably improved the treatment outcomes. MPT (MP + thalidomide), VMP (MP + bortezomib), and MPR-R (MP + lenalidomide) regimens are currently regarded as the new standards of care for elderly patients with multiple myeloma. The prognosis for multiple myeloma is determined by numerous factors, all of which should be considered when choosing the initial therapy. This review covers the new strategies based on the current studies being conducted that are aimed at optimizing treatment outcomes in the patients with newly diagnosed multiple myeloma.

Keywords: multiple myeloma, bortezomib, thalidomide, lenalidomide, treatment, complete remission, overall survival, neuropathy, autologous stem cell transplantation

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Multiple myeloma (pathogenesis, clinical features, diagnosis, differential diagnosis). Part I

REVIEWS , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, Saint Petersburg, Russian Federation

ABSTRACT

Multiple myeloma (MM) is a malignancy characterized by bone marrow infiltration with plasma cell and extensive skeletal bone destruction resulting in bone pain and fractures. This review presents typical laboratory findings and clinical presentation of multiple myeloma. Multiple myeloma is definite when the following hallmarks are present: ³ 10% of clonal plasma cells in the bone marrow, M protein in serum or urine (except nonsecretory myeloma), hypercalcemia, renal insufficiency, anemia, or osteolytic lesions in skeletal bones. Monoclonal (M) proteins are detected using serum protein electrophoresis and immunofixation. In addition, urine protein electrophoresis and immunofixation or a serum free light-chain assay are essential. The International Staging System classifies MM patients into three groups of risk — standard, intermediate, or high — depending on the b2-microglobulin and albumin serum levels. The presence of any one of the following indicates high-risk myeloma: a 13q deletion or hypodiploidy on metaphase cytogenetic studies, a 17p deletion, immunoglobulin heavy-chain translocations t(4;14) or t(14;16), or a plasma cell labeling index ³ 3%.

This review presents laboratory findings and clinical manifestations of monoclonal gammopathy of undetermined significance, asymptomatic myeloma (‘smouldering myeloma’), nonsecretory myeloma, solitary bone plasmacytoma, extramedullary plasmacytoma, plasma cell leukemia, Waldenstrom’s macroglobulinemia, amyloidosis, and other diseases.

Keywords: multiple myeloma, monoclonal gammopathy of undetermined significance, asymptomatic myeloma, M protein, clonal plasma cells.

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Selection of patients for iron-chelating therapy

COMPLICATIONS OF SUPPORTIVE THERAPY , , , , , ,

S.V. Gritsaev, B. Davaasambuu, N.A. Romanenko, and K.M. Abdulkadyrov

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

ABSTRACT

Emergence of iron aggressive forms in patients with hematological or oncohematological diseases is potentially life-threatening. This can be caused by several situations: multiple allogeneic RBC transfusions, increased intestinal absorption of iron, or damaging effects of chemotherapeutic agents. The objective of the study was to identify candidates for iron-chelating therapy. The data on 727 patients with screening blood tests were analyzed. The highest serum ferritin level was revealed in patients with thalassemia, PMF, or MDS. They received 80, 37, or 35 RBC transfusions, respectively. The lowest serum ferritin levels were found in patients with CLL or hemolytic anemia that received lesser number of RBC transfusions, namely, 18.5 and 16.5, respectively. The correlation between serum ferritin level and the total number of RBC transfusions was revealed: r = 0.462; p = 0.000. We concluded that iron-chelating therapy is primarily indicated to the patients with MDS or PMF in whom the high serum ferritin level is due to excessive post-transfusion iron.

Keywords: myelodysplastic syndromes, primary myelofibrosis, thalassemia, acute leukemia, multiple myeloma, serum ferritin, allogeneic RBC transfusions.

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Minimally invasive surgical techniques in hematological malignancies with spinal involvement

SURGICAL TECHNOLOGIES IN LYMPHOID TUMORS , , ,

A.K. Valiev, A.V. Sokolovsky, A.S. Nered, and E.R. Musaev

N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

The current statistical data show an increased number of malignancies with skeletal bones involvement, that comprise in average 1.5–2 % of all malignancies. Among them according to some authors, the most common, in decreasing order of incidence, are: multiple myeloma (35–50 %), osteosarcomas (20–30 %), chondrosarcomas (10–17 %), Ewing’s sarcoma (6–12 %), and lymphomas (3–7 %). Therefore, the issue of treating pathological fractures of the spine in multiple myeloma or lymphoma becomes more pressing, since the number of such patients is increasing. Existing surgical minimally invasive techniques enable to increase the quality of life in these groups and start special conservative treatment as soon as possible.

Keywords: spine, pathological fracture, multiple myeloma, lymphomas

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