This phase III, randomized, controlled study evaluates the bortezomib-dexamethasone plus oral cyclophosphamide regimen versus bortezomib and dexamethasone in patients with primary refractory or relapsed multiple myeloma. Kropff M et al. Ann Hematol  2017. DOI:10.1007/s00277-017-3065-z

An expert review of current treatment options for relapsed/refractory multiple myeloma, the mechanism of action of panobinostat, and how panobinostat fits into the current therapeutic landscape. San-Miguel JF, Einsele H, & Moreau P. Adv Ther 2016; 33: 1896–1920. doi:10.1007/s12325-016-0413-7

​​​​​​​Based on a comprehensive literature search, Lipe et al. analyze the most current literature and to provide recommendations for maintenance therapy in multiple myeloma. Summary points Multiple myeloma (MM) is the second most common type of blood cancer and remains incurable despite advances in therapy. Therapy for MM is typically administered in a phased approach, which often consists of initial induction therapy, consolidation, and maintenance therapy. There is strong evidence to suggest that maintenance therapy with bortezomib and lenalidomide improves progression-free survival. Data regarding overall survival (OS) is more variable, but at least three trials suggest improved OS with maintenance therapy. As a result of the data, the authors recommend continuous maintenance therapy with lenalidomide/dexamethasone or bortezomib for the transplant-ineligible population (GRADE 2A); the choice of maintenance therapy should be matched to the induction regimen. For patients receiving both lenalidomide and bortezomib during induction, maintenance therapy should be guided by patient preference, toxicity profile, and risk-stratification of disease. For transplant-eligible patients, stratified maintenance therapy should be based on risk features and depth of response. For standard risk patients who have achieved a sustained complete response (CR), lenalidomide maintenance for 2 years (GRADE 2B) is recommended. For patients with less than a CR, indefinite maintenance therapy with lenalidomide (GRADE 2B) is advised. If patients are intolerant or resistant to lenalidomide, bortezomib maintenance should be used (GRADE 2B). A combined bortezomib–lenalidomide or bortezomib-based maintenance strategy for high-risk patients (GRADE 2C) is also recommended. Lipe et al.​​​​​​​  Blood Cancer J  2016; 6: e485. doi: 10.1038/bcj.2016.89

The focus of this review is a critical analysis of combinations of novel agents in the treatment of newly diagnosed multiple myeloma in both transplant eligible and ineligible patients. Summary points Multiple myeloma (MM) is the second most common hematologic malignancy, accounting for 1% of neoplastic diseases and 13% of hematologic cancers, and predominantly affects the elderly. The introduction of novel therapies such as thalidomide, lenalidomide, and bortezomib for the treatment of MM in the last 15 years has drastically improved progression-free survival (PFS), overall survival (OS), and quality of life for patients with MM. In transplant-eligible patients, the three-drug regimens CyBorD, RVD, and BiRD appear to be the most effective with tolerable adverse effect profile and PFS benefit. Carfilzomib in combination with lenalidomide and dexamethasone has been shown to induce deep responses to the point of negative minimal residual disease state on flow cytometry. In transplant-ineligible patients, continuous use of two-drug regimens bortezomib/dexamethasone or lenalidomide/dexamethasone has shown superior overall response and PFS with enhanced tolerability compared with three-drug regimens. New agents for the treatment of MM are under investigation in the relapsed or refractory disease state. As these agents are approved and move to the upfront setting, more exciting and promising results for both the transplant eligible and ineligible patient population will be seen. Runcie KD & Mark TM. Curr Hematol Malig Rep 2015; 10: 388–394. doi:10.1007/s11899-015-0282-1

The authors summarize the positioning of bortezomib, a first-generation proteasome inhibitor, and second-generation proteasome inhibitors in leukemia treatment from a preclinical and clinical perspective. Cloos J, Roeten MS, Franke NE et al. Cancer Metastasis Rev 2017. doi:10.1007/s10555-017-9699-4

The authors examine in a real-world practice setting whether the proteasome inhibitor bortezomib and immunomodulatory drugs lenalidomide and thalidomide are effective in prolonging overall survival in newly diagnosed multiple myeloma. Chen Y, Lairson DR, Chan W, Du XL. Med Oncol 2017;34:153. doi:10.1007/s12032-017-1001-7

This review discusses current multiple myeloma treatment options, effective symptom management approaches, and practical strategies for supportive care. Summary points Recent therapeutic advances have significantly improved overall survival in patients with multiple myeloma (MM), with a concomitant increase in susceptibility to disease- and treatment-related symptoms. Current therapeutic regimens for relapsed/refractory MM include proteasome inhibitors (eg, bortezomib, carfilzomib) and immunomodulatory agents (eg, thalidomide, lenalidomide, pomalidomide), alone or in combination with chemotherapy or corticosteroids. Toxicities associated with agents and combination regimens used in the treatment of MM include myelosuppression, venous thromboembolism, peripheral neuropathy, infections, fatigue, gastrointestinal disorders, and/or cardiac events. Treatment-specific tools and clinical assessments can be useful for optimizing dosing and schedule adjustments to increase therapy duration, and implementing supportive care strategies (such as growth factors, transfusional support, intravenous hydration, bisphosphonates, and antiviral therapies) to manage treatment-related symptoms. Effective management of the patient with MM requires knowledge of the disease and of treatment-associated adverse events in addition to preventative measures, supportive care strategies, and management of comorbidities. Patient education and individualized survivorship plans can play a role in achieving maximal patient responses to treatment. Improved survival after MM diagnosis has led to increased patient susceptibility to other diseases and comorbidities due to advanced age, thus optimal symptom management will be important to maximize quality of life for patients in addition to disease control and survival. Colson K. Support Care Cancer 2015; 23: 1431–1445. doi:10.1007/s00520-014-2552-1

In the GEM2005MAS65 trial, patients were randomized in a 2x2 design to either bortezomib/melphalan/prednisone (VMP) or bortezomib/thalidomide/prednisone (VTP) for induction and consolidation. 26  Patients were then randomized to maintenance therapy with bortezomib/prednisone (VP) vs bortezomib/thalidomide (VT).

This articles reviews the clinical efficacy of immunomodulatory drugs, their structure-function relationship, molecular mechanisms of action, and associated second primary malignancies and thrombosis. Holstein SA & McCarthy PL. Drugs 2017; 77: 505–520. doi:10.1007/s40265-017-0689-1

This review analyzes the latest advances and challenges resulting from the introduction of proteasome inhibitors into the clinical setting for patients with multiple myeloma. Nat Rev Clin Oncol 2017. doi:10.1038/nrclinonc.2016.206

This fact, alongside the drug’s distinct mode of action compared with conventional cytotoxics, was noted in initial PPTP testing, suggesting further investigation of bortezomib combined with existing therapies to increase its clinical relevance.

A larger single arm phase II trial (MCL-001) enrolled 134 patients, including many who were refractory to bortezomib 51 .