Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens

Niesvizky, Rubén; Flinn, Ian W.; Rifkin, Robert M.; Gabrail, Nashat; Charu, Veena; Clowney, Billy; Essell, James; Gaffar, Yousuf; Warr, Thomas A.; Neuwirth, Rachel; Zhu, Yanyan; Elliott, Jennifer; Esseltine, Dixie‐Lee; Niculescu, Liviu; Reeves, James A.

doi:10.1200/jco.2014.58.7618

Cited by 138 publications

(134 citation statements)

References 29 publications

(7 reference statements)

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“…In a randomized open-label study, newly diagnosed patients with myeloma who were ineligible for stem cell transplant because of age (≥65 years), comorbidities, or personal preference were randomly assigned 1:1:1 to receive eight 21-day cycles of VD, VTD, or VMP induction followed by five 35-day cycles of maintenance with single-agent intravenous bortezomib 1.6 mg/m 2 on days 1, 8, 15, and 22 31. Median PFS with VD, VTD, and VMP was 14.7, 15.4, and 17.3 months, respectively; median OS was 49.8, 51.5, and 53.1 months, with no significant differences among treatments for either end point (global P = 0.46 and P = 0.79, respectively).…”

Section: Bortezomib In Special Situationsmentioning

confidence: 99%

Update on the optimal use of bortezomib in the treatment of multiple myeloma

Mohan

Matin

Davies

2017

CMAR

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The proteasome inhibitor (PI) “bortezomib” has now been in routine clinical practice for over a decade. It is now considered an important backbone therapy for all stages of the disease, and data continue to grow to support its use in newly diagnosed patients, relapsed and relapsed/refractory disease, maintenance therapy, high risk, and renal failure. Much has been learnt about the most clinically effective way of delivering therapy, with patients often benefiting more from a triplet bortezomib combination compared to a doublet combination. It is well tolerated and can be administered in the outpatient setting with manageable toxicity. The key to good results is managing side effects so that patients remain on therapy with minimal interruptions. Therefore, proactive management of peripheral neuropathy and thrombocytopenia is advised using dose delay and reduction strategies. The recent introduction of second- and third-generation PIs with different chemical and biological properties has resulted in a plethora of new clinical studies and has confirmed the ongoing role of this class of drugs in future myeloma therapy.

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Section: Bortezomib In Special Situationsmentioning

confidence: 99%

Update on the optimal use of bortezomib in the treatment of multiple myeloma

Mohan

Matin

Davies

2017

CMAR

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“…According to the P -values, bortezomib-based regimens (VD, VTD, VMP, VMPS and VMPT-VT) were also associated with promising antimyeloma activity, while these regimens had similar antimyeloma activities. Previous studies suggested that melphalan might be the best partner for bortezomib-based induction regimen in elderly patients with untreated MM when the efficacy, toxicities, and costs were taken into consideration 29,40…”

Section: Discussionmentioning

confidence: 99%

Comparing efficacy and survivals of initial treatments for elderly patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

Chen

et al. 2016

OTT

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ObjectiveThe aim of this study was to evaluate the efficacy and clinical outcome of initial therapies for elderly patients with multiple myeloma (MM).MethodsRandomized controlled trials (RCTs) were obtained through a comprehensive search. Response rate, progression-free survival (PFS) and overall survival (OS) were the interested outcome measures. Network meta-analysis (NMA) using graph theory methodology to construct an NMA model, and sensitivity analysis were performed.ResultsNineteen RCTs containing 7,235 participants and 17 treatments were included in the NMA. As compared to the classic melphalan plus prednisone (MP) regimen, the majority of other initial regimens showed higher rates of complete response/near complete response, overall response rate (ORR) and better PFS as well as OS. These four outcomes favored the two lenalidomide plus dexamethasone regimens (continuous lenalidomide and 18 cycles of lenalidomide plus dexamethasone), especially continuous lenalidomide plus dexamethasone regimen, over the majority of other regimens including the two established standard treatments (MP plus thalidomide or bortezomib) for elderly patients with newly diagnosed MM.ConclusionContinuous lenalidomide plus dexamethasone ranked as the best regimen in terms of ORR and OS for the treatment of elderly patients with newly diagnosed MM.

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“…VTD was associated with more adverse events and worse HRQoL. 52 Four-drug therapy with MPT + bortezomib (VMPT) followed by VT maintenance (VMPT-VT) versus VMP resulted in higher OR (89% versus 81%, p=.01), but greater grade 3/4 non-hematologic toxicities in the 4-drug arm (46% versus 33%, p=.003). 4 Other combinations, such as a modified combination of weekly bortezomib, reduced-dose lenalidomide and dexamethasone (“RVD lite”), are being explored, with encouraging toxicity profiles.…”

Section: Initial Therapymentioning

confidence: 96%

Management of multiple myeloma in older adults: Gaining ground with geriatric assessment

Wildes

Campagnaro

2017

Journal of Geriatric Oncology

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Multiple myeloma increases in incidence with age. With the aging of the population, the number of cases of multiple myeloma diagnosed in older adults each year will nearly double in the next 20 years. The novel therapeutic agents have significantly improved survival in older adults, but their outcomes remain poorer than in younger patients. Older adults may be more vulnerable to toxicity of therapy, resulting in decreased dose intensity and contributing to poorer outcomes. Data are beginning to emerge to aid in identifying which individuals are at greater risk for toxicity of therapy; comorbidities, functional limitations and age over 80 are among the factors associated with greater risk. Geriatric assessment holds promise in the care of older adults with multiple myeloma, both to allow modification of treatment to prevent toxicity, and to identify vulnerabilities that may require intervention. Emerging treatments with low toxicity and attention to individualizing therapy based on geriatric assessment may aid in further improving outcomes in older adults with multiple myeloma.

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Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens

Abstract: Although all bortezomib-containing regimens produced good outcomes, VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice.

Cited by 138 publications

References 29 publications

Update on the optimal use of bortezomib in the treatment of multiple myeloma

Update on the optimal use of bortezomib in the treatment of multiple myeloma

Comparing efficacy and survivals of initial treatments for elderly patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

Management of multiple myeloma in older adults: Gaining ground with geriatric assessment

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