The power of proteasome inhibition in multiple myeloma.

INTRODUCTION: Proteasome inhibitors (PIs) are therapeutic backbones of multiple myeloma treatment, with PI-based therapies being standards of care throughout the treatment algorithm. Proteasome inhibition affects multiple critical signaling pathways in myeloma cells and interacts synergistically with mechanisms of action of other conventional and novel agents, resulting in substantial anti-myeloma activity and at least additive effects. Areas covered: This review summarizes the biologic effects of proteasome inhibition in myeloma and provides an overview of the importance of proteasome inhibition to the current treatment algorithm. It reviews key clinical data on three PIs, specifically bortezomib, carfilzomib, and ixazomib; assesses ongoing phase 3 trials with these agents; and looks ahead to the increasingly broad role of both approved PIs and PIs under investigation in the frontline and relapsed settings. Expert commentary: Progress to date with PIs in multiple myeloma has been impressive, but there remain unmet needs and challenges, as well as increasing opportunities to optimize the use of these agents. Understanding discrepancies between PIs in terms of efficacy and safety profile is a key goal of ongoing research, along with proteomics-based efforts to identify potential biomarkers of sensitivity and resistance, thereby enabling increasingly personalized treatment approaches in the future.

Multiple Myeloma Masquerading as Ovarian Carcinosarcoma Metastases: A Case Report and Review of the Approach to Multiple Myeloma Screening and Diagnosis.

Multiple myeloma is the most common plasma cell dyscrasia and causes 2% of all cancer deaths in Western countries. Ovarian carcinosarcomas are very rare gynecological malignancies and account for only 1-2% of all ovarian tumors. In this case, we report a 67-year-old woman with known relapsed ovarian carcinosarcoma who presented with headache and neck pain. She was found to have new lytic lesions in the cranial and thoracic regions. While these lesions were assumed to be metastases, a diligent approach detected an M-spike on serum protein electrophoresis and a monoclonal gammopathy with immunoglobulin G lambda monoclonal immunoglobulin on immunofixation. A bone marrow biopsy confirmed the diagnosis of multiple myeloma. To our knowledge, this is the first ever reported case of concomitant multiple myeloma and ovarian carcinosarcoma. Our case highlights the utmost importance of a systematic approach to lytic lesions and emphasizes the need to consider secondary malignancies in the evaluation of possible metastases. We used the International Myeloma Working Group guidelines for screening and diagnosing multiple myeloma, and we provide a thorough review of this updated approach.

Bortezomib in plasmablastic lymphoma: A glimpse of hope for a hard-to-treat disease.

Plasmablastic lymphoma (PBL) is a rare and hard to treat disease. With current standard chemotherapeutic regimens, PBL is associated with a median overall survival of 12-15 months. We performed a systematic review of the literature through March 31, 2017 looking for patients with a diagnosis of PBL who were treated with bortezomib, alone or in combination. We identified 21 patients, of which 11 received bortezomib in the frontline setting and 10 received bortezomib in the relapsed setting. Eleven patients were HIV-positive and 10 were HIV-negative. The overall response rate to bortezomib-containing regimens was 100% in the frontline setting and 90% in the relapsed setting. Furthermore, the 2-year overall survival of patients treated upfront was 55%, and the median OS in relapsed patients was 14 months. Although the sample size is small, we believe our results are encouraging and should serve as rationale to investigate bortezomib-based regimens in patients with PBL.