James R Berenson

..A randomized trial has established that bortezomib not only improves response rates but also prolongs the lives of patients with multiple myeloma who are not candidates for high-dose chemotherapy...

..A number of other types of new anti-bone-resorptive agents are also in early clinical development...

..With these simple precautions, intravenous bisphosphonate therapy is safe for long-term use and provides durable treatment benefits...

..Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma...

..Bortezomib has shown synergy with melphalan in preclinical models. We assessed the safety, tolerability, and response rate in a dose-escalation study of this combination for relapsed or refractory multiple myeloma patients...

..Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model...

..These in vitro and in vivo results suggest that addition of ATO to other antimyeloma agents may result in improved outcomes for patients with relapsed or refractory MM...

..These studies provide strong preclinical rationale for further development of this novel PI in the treatment of MM as a monotherapy as well as combined with either melphalan or bortezomib...

..LBH589 with melphalan or doxorubicin also showed significantly enhanced anti-myeloma activity in vivo. These findings provide the basis for clinical development of these combination therapies...

..In conclusion, bortezomib plus melphalan is a steroid- and immunomodulatory drug-free regimen that may provide a treatment alternative for elderly patients and patients with significant comorbidity...

..This modified regimen of dexamethasone, bortezomib and PLD shows improved tolerability and safety while maintaining a high response rate when compared to standard treatment with these agents in the frontline setting...

..These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients...

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..The favorable results obtained from the three xenograft studies suggest that delanzomib in combination with dexamethasone and lenalidomide should be explored for the treatment of MM...

..We conducted a single-arm, multicentre phase 2 study to evaluate bortezomib, ascorbic acid and melphalan (BAM) for patients with newly diagnosed multiple myeloma (MM)...

..One patient discontinued this regimen due to an adverse event (grade II PN). DVD appears to represent a well-tolerated regimen with a high response rate for the treatment of R/R MM patients...

..This open-label, phase I dose-escalation study assessed the safety, tolerability, and initial efficacy of Samariam 153 (153Sm)-lexidronam/bortezomib combination therapy for patients with relapsed/refractory multiple myeloma...

..Because the expression of this protein is very limited in normal adult tissues, PTN may represent a new target for the treatment of MM...

..Our results suggest that vasculogenesis in human MM may develop from tumoral production of PTN, which orchestrates the transdifferentiation of monocytes into VECs...

..This steroid-free regimen was effective and well tolerated in this heavily pretreated group. These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM...

..This review highlights the newest approaches with already approved drugs for treating this common B-cell malignancy...

..This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss...

..This review will focus on the clinical trials that have reinforced the use of these new agents. Also, we will briefly take a look at the newer drugs making their way out of the laboratory and into early phase studies...

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..On the basis of these encouraging results, clinical studies are underway to test the efficacy of PS-341 and chemotherapeutic agents as combination therapy in treating patients with refractory and relapsed MM...

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..Our new clinically relevant SCID models of human myeloma should greatly facilitate drug development and enable novel therapies to quickly move from the laboratory to the clinic...

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..The use of bisphosphonates has focused on their antibone resorptive effects but recent studies have shown that these drugs also possess a variety of antitumor effects in the laboratory that are now being observed in clinical trials...

..As our understanding of the pathophysiology of myeloma bone disease continues to increase, new target therapies will continue to emerge offering new and more advanced options for the management of myeloma bone disease...

..Because INNO-206 has not been previously evaluated in any hematologic malignancy, we determined its anti-multiple myeloma effects...

..Once these tumors are generated, they can be used to evaluate novel anti-MM agents and other therapies...

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..This review aims to summarize recent advances in the mechanisms through which the activation of the transcription factor NF-kappaB contributes to the pathogenesis of multiple myeloma...

..us.zometa.com) in reduction of pain, reduction of SREs and survival. Moreover, recent data suggest direct and indirect antimyeloma activity of pamidronate and zoledronic acid...

..Ongoing studies will help further refine and optimize the timing and duration of BP therapy in patients with myeloma bone disease...

..Although ONJ and renal deterioration may infrequently occur with ZOL, most patients do not experience worsening of these conditions with ongoing treatment with this bisphosphonate...

..The activity and tolerability observed in clinical studies promise to make arsenic-based chemotherapy a viable treatment option for patients whose disease does not respond to or who cannot tolerate other chemotherapy regimens...

..As our understanding of the pathophysiology of myeloma bone disease continues to grow, new target therapies will continue to emerge, offering new and more advanced options for the management of myeloma bone disease...

..The following consensus statement outlines the conclusions and marks the first time that a consensus statement for the screening and treatment of MGUS has been clearly stated...

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..001). These results suggest that serum PTN may be a new biomarker for monitoring the disease status and therapeutic response of MM patients...

..With proper diagnostic and treatment strategies, these patients will experience improved outcomes and quality of life...

..Furthermore, zoledronic acid has a safety profile similar to that of pamidronate and other intravenous bisphosphonates. Thus, zoledronic acid represents a significant therapeutic advance in the clinical management of HCM...

..However, federal funding for cancer prevention is less than half that of cancer treatment. As a result of its enormous potential for extending life, cancer prevention warrants increased funding and support from federal funding agencies...

..Thus, these results suggest that inhibition of NF-kappaB with PS-341 may overcome chemoresistance and allow doses of chemotherapeutic agents to be markedly reduced with antitumor effects without significant toxicity...

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..The priority area of needed future research is maintenance therapy posttransplantation with nothing versus interferon alpha versus other agents such as corticosteroids or thalidomide or its derivatives...

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..Thus, 50 mg, oral, alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy. (Blood. 2002;99:3163-3168)..

..Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date...

..The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production...

..BACKGROUND AND OBJECTIVEs: The efficacy and safety of added dexamethasone were assessed in patients with relapsed and/or refractory multiple myeloma who had a suboptimal response to bortezomib alone...

..The aim of this review is to improve our understanding of bone markers as a clinical tool for the management of malignant bone disease in patients with MM...

..The results also highlight the anti-angiogenic properties of thalidomide and CC-5013 and further elucidate possible mechanisms of their effectiveness against MM. (Blood. 2005;105:3286-3294)...

..The conclusions reached during the 2-day meeting are summarized in this article and presented in more detail in the individual articles and accompanying discussion sessions that comprise the conference proceedings...

..In addition, we detected two polymorphisms in the IkappaBalpha gene that have not been previously reported. Together, these results provide the basis for future evaluation the IkappaBalpha/NF-kappaB pathway in MM patients...

..49, 95% confidence interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower relapse risk than autotransplants in MM, suggesting that graft composition may impact outcomes following high-dose chemotherapy...