The Changing Landscape of Myeloma Therapy

Cavo, Michèle; Baccarani, Michele

doi:10.1056/nejme058322

Cited by 29 publications

(19 citation statements)

References 13 publications

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“…The 5TGM1 model has already proved to be predictive of efficacy in preclinical drug testing (8) and these new capabilities suggest the potential utility of the Radl 5TGM1 model in large-scale anticancer drug screening. This should accelerate discovery, evaluation, and development of novel therapies for myeloma (4).…”

Section: Resultsmentioning

confidence: 99%

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

Oyajobi

Munoz

Käkönen

et al. 2007

Molecular Cancer Therapeutics

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Development of new therapies for myeloma has been hindered by the lack of suitable preclinical animal models of the disease in which widespread tumor foci in the skeleton can be detected reliably. Traditional means of detecting skeletal tumor infiltration such as histopathology are cumbersome and labor-intensive and do not allow temporal monitoring of tumor progression or regression in response to therapy. To resolve this problem, we modified the Radl 5TGM1 model of myeloma bone disease such that fluorescent myeloma tumors can be optically imaged in situ. Here, we show that murine myeloma 5TGM1 tumor cells, engineered to express enhanced green fluorescent protein (eGFP; 5TGM1-eGFP cells), can be imaged in a temporal fashion using a fluorescence illuminator and a charge-coupled device camera in skeletons of live C57BL/ KaLwRij mice. High-resolution, whole-body images of tumor-bearing mice revealed that myeloma cells homed almost exclusively to the skeleton, with multiple focal

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Section: Resultsmentioning

confidence: 99%

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

Oyajobi

Munoz

Käkönen

et al. 2007

Molecular Cancer Therapeutics

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“…The combination of thalidomide and corticosteroids is synergistic in relapsed 28,29 and newly diagnosed 30,31 disease. Thalidomidedexamethasone as initial therapy is superior to dexamethasone alone in terms of response rates and PFS, but its impact on OS is unclear.…”

Section: Lenalidomide Combinationsmentioning

confidence: 99%

“…A key characteristic thalidomide shares with corticosteroids is lack of myelosuppression. 8,29 Single-agent thalidomide is a reasonable option in patients with relatively low-grade disease, especially if marrow function is compromised.…”

Section: Lenalidomide Combinationsmentioning

confidence: 99%

How I treat elderly patients with myeloma

Mehta

Cavo²,

Singhal

2010

Blood

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The clinical approach to older patients with myeloma has to be modified to take into account comorbidities and the likelihood of higher treatment-related toxicity. Individualization of management and adequate supportive therapy are important to obtain the best response while minimizing adverse effects. Corticosteroids, novel agents, conventional cytotoxic agents, and high-dose chemotherapy with autotransplantation (modalities used in younger patients) are also used in older patients, although the elderly undergo transplantation less frequently. The sequential use of active agents singly and in different combinations has improved response rates and survival of all patients with myeloma, including the elderly. (Blood. 2010;116(13):2215-2223)

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“…3 The widespread use of ASCT and the introduction into clinical practice of the novel agents bortezomib and the immunomodulatory derivatives (IMiDs) thalidomide and lenalidomide have significantly contributed to major advances in MM therapy and prognosis. 4,5 Thalidomide or bortezomib combined with melphalan and prednisone represent new standards of care for elderly, transplantationineligible MM patients. [6][7][8] In this setting, lenalidomide in combination with low-dose dexamethasone is an alternative treatment option.…”

Section: Introductionmentioning

confidence: 99%

International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation

Cavo¹,

Rajkumar

Palumbo

et al. 2011

Blood

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288

202

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The role of high-dose therapy followed by autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) continues to evolve in the novel agent era. The choice of induction therapy has moved from conventional chemotherapy to newer regimens incorporating the immunomodulatory derivatives thalidomide or lenalidomide and the proteasome inhibitor bortezomib. These drugs combine well with traditional therapies and with one another to form various doublet, triplet, and quadruplet regimens.Up-front use of these induction treatments, in particular 3-drug combinations, has affected unprecedented rates of complete response that rival those previously seen with conventional chemotherapy and subsequent ASCT. Autotransplantation applied after novel-agent-based induction regimens provides further improvement in the depth of response, a gain that translates into extended progression-free survival and, potentially, overall survival. High activity shown by immunomodulatory derivatives and bortezomib before ASCT has recently led to their use as consolidation and maintenance therapies after autotransplantation. Novel agents and ASCT are complementary treatment strategies for MM. This article reviews the current literature and provides important perspectives and guidance on the major issues surrounding the optimal current management of younger, transplantation-eligible MM patients. (Blood. 2011; 117(23):6063-6073) IntroductionMultiple myeloma (MM) is a disease of the elderly. Overall, only 35% of the patients are younger than 65 years at the time of diagnosis, whereas the remaining two-thirds are older. 1 Age is an independent prognostic factor in MM 2 and, importantly, provides a major criterion by which patients can be considered eligible to tolerate high-dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT). Over the last decade, the survival of patients with newly diagnosed MM, particularly those younger than 60 years, has significantly improved. 3 The widespread use of ASCT and the introduction into clinical practice of the novel agents bortezomib and the immunomodulatory derivatives (IMiDs) thalidomide and lenalidomide have significantly contributed to major advances in MM therapy and prognosis. 4,5 Thalidomide or bortezomib combined with melphalan and prednisone represent new standards of care for elderly, transplantationineligible MM patients. [6][7][8] In this setting, lenalidomide in combination with low-dose dexamethasone is an alternative treatment option. 9 In younger patients, the novel agents have been incorporated into the therapeutic algorithm along with ASCT to improve clinical outcomes. [10][11][12] In particular, these drugs have been used as part of induction therapy before ASCT and as consolidation/maintenance after autotransplantation. This manuscript from the International Myeloma Working For personal use only. on May 13, 2018. by guest www.bloodjournal.org From Group (IMWG) presents an overview of the most recent studies of novel agents combined with ASCT an...

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The Changing Landscape of Myeloma Therapy

Cited by 29 publications

References 13 publications

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

How I treat elderly patients with myeloma

International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation

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