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While survival times have increased over the last decade, most patients with multiple myeloma (MM) eventually relapse and become refractory to therapy. The treatment of patients with relapsed and/or refractory MM is frequently further complicated by the presence of pre-existing comorbidities that arise from an advanced disease state and of toxicities stemming from prior antimyeloma treatment. Carfilzomib and pomalidomide have recently been approved for the treatment of patients with relapsed and refractory MM. While these agents represent important additions to the available treatment options, the identification of patients who may best benefit from the use of each of therapy is still being investigated. A number of patient-related and disease-related factors may impact treatment efficacy and/or tolerability, and the clinical presentation and medical history of each patient must be carefully considered to optimize treatment. Here, we review results from carfilzomib and pomalidomide clinical trials in patients with relapsed and/or refractory MM who also have baseline comorbidities or treatment-induced or disease-induced complications (including the presence of renal impairment, cardiac risk factors, peripheral neuropathy, or high-risk chromosomal abnormalities) to evaluate the safety and efficacy of the two agents in these difficult-to-treat patients and to provide treatment recommendations specific to each scenario. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second most common hematological malignancy, with an incidence of 6/100 000 in Europe. Interactions between myeloma cells and the microenvironment are essential for MM cell survival. Better knowledge of disease biology has led to the introduction of novel agents for the management of myeloma patients. Patients with asymptomatic MM may remain stable for a long time without any therapy, and treatment is needed only in symptomatic disease. Patients who are eligible for high-dose therapy and autologous stem cell transplantation (ASCT) are usually treated with bortezomib- or immunomodulatory drug (IMiD)-based regimens as induction therapy pre-ASCT. In elderly patients, the combination of melphalan and prednisone with either thalidomide (MPT) or bortezomib (MPV) is considered as the standard of care in this setting. Novel agent-based therapies are used for the management of relapsed/refractory disease. However, previous therapies, age, comorbidities and drug safety have to be taken into consideration before deciding the appropriate therapy for patients with relapsed/refractory myeloma. Patients with renal impairment or with extended bone disease may be treated with bortezomib-based regimens, while patients with pre-existing peripheral neuropathy may be treated with lenalidomide-based combinations. Maintenance therapy with thalidomide can be administered post-ASCT; however, caution is needed due to thalidomide toxicity. [ABSTRACT FROM AUTHOR]

Background Activin-A is a transforming growth factor -β superfamily member, which seems to be implicated in the biology of osteolytic disease in multiple myeloma. Design and methods Circulating activin-A was evaluated in 98 newly diagnosed myeloma patients (85 with symptomatic disease), in 40 patients with relapsed myeloma before and after four cycles of lenalidomide and dexamethasone (RD), in 27 healthy controls and in 10 monoclonal gammopathy of undetermined significance patients. Results Patients with newly diagnosed symptomatic myeloma had increased circulating activin-A compared with controls (P < 0.001), while patients with relapsed disease had elevated activin-A even compared with symptomatic patients at diagnosis (P < 0.001). High activin-A correlated with advanced International Staging System stage (P = 0.002), increased bone resorption (P < 0.001) and extensive bone disease (P = 0.03). Low levels of activin-A (<442 pg/ml) were associated with superior median overall survival: not reached versus 59 months (P = 0.04), while activin-A inversely correlated with survival as a continuous variable (P < 0.001). RD did not alter circulating activin-A after four cycles of treatment, even in responders. Conclusions High circulating activin-A correlates with advanced features of myeloma, supporting the rationale for the use of activin-A antagonists, such as sotatercept in myeloma. The inability of RD to reduce activin-A reveals RD as a good candidate for combination therapies with activin-A antagonists in myeloma. [ABSTRACT FROM AUTHOR]