Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial

Merz, Maximilian; Salwender, Hans; Haenel, Mathias; Elias, K.; Bertsch, Uta; Kunz, Christina; Hielscher, Thomas; Blau, Igor Wolfgang; Scheid, Christof; Hose, Dirk; Seckinger, Anja; Jauch, Anna; Hillengaß, Jens; Raab, Marc S.; Schurich, Baerbel; Munder, Markus; Schmidt‐Wolf, Ingo G.H.; Gerecke, Christian; Lindemann, Hans Walter; Zeis, Matthias; Weisel, Katja; Duerig, Jan; Goldschmidt, Hartmut

doi:10.3324/haematol.2015.124347

Cited by 64 publications

(45 citation statements)

References 22 publications

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“…25 The subcutaneous route is equally effective as the intravenous route and associated with a considerably lower risk of peripheral neuropathy. 63–66 Bortezomib, together with dexamethasone, can be combined with cyclophosphamide, 67 thalidomide, 68 and lenalidomide, 69 resulting in highly active regimens for relapsed multiple myeloma. The risk of neuropathy is increased when bortezomib is combined with thalidomide.…”

Section: Drugs Approved For Therapy For Multiple Myelomamentioning

confidence: 99%

Therapy for Relapsed Multiple Myeloma

Dingli

Ailawadhi

Bergsagel

et al. 2017

Mayo Clinic Proceedings

120

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Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy. A group of physicians at Mayo Clinic with expertise in the care of patients with multiple myeloma regularly evaluates the evolving literature on the biology and therapy for multiple myeloma and issues guidelines on the optimal care of patients with this disease. In this article, the latest recommendations on the diagnostic evaluation of relapsed multiple myeloma and decision trees on how to treat patients at various stages of their relapse (off study) are provided together with the evidence to support them.

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Section: Drugs Approved For Therapy For Multiple Myelomamentioning

confidence: 99%

Therapy for Relapsed Multiple Myeloma

Dingli

Ailawadhi

Bergsagel

et al. 2017

Mayo Clinic Proceedings

120

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“…2 Since subcutaneous (SC) administration reduces rates of bortezomib-induced neuropathy (BiPN), [3][4][5] nowadays bortezomib is mainly given subcutaneously in clinical trials and in general practice. Only limited data are available on risk factors for BiPN in the era of SC bortezomib.…”

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confidence: 99%

Peripheral neuropathy associated with subcutaneous or intravenous bortezomib in patients with newly diagnosed myeloma treated within the GMMG MM5 phase III trial

et al. 2016

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“…Patient characteristics are summarized in Online Supplementary Table S1; see details. 9,10 Methods used to measure Ig concentrations and subtypes are described elsewhere 13 and in Supplementary material. CAs were identified for available samples using fluorescence in situ hybridization (FISH) techniques.…”

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confidence: 99%

“…We carried out a systematic analysis of Ig and FLC subtypes and their serum levels in relation with common CAs using data on 523 patients recruited in German-Speaking Myeloma Multicenter Group (GMMG)-MM5 trial. 9,10 For purpose of replication, an independent cohort of 325 cases from GMMG-HD4 trial was obtained. 11,12 Blood samples were collected prior to treatment initiation in the above trials, coordinated by University Clinic Heidelberg.…”

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confidence: 99%

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels

et al. 2018

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aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels. Haematologica. 2018; 103:xxx doi:10.3324/haematol.2017.184226 Publisher's Disclaimer. As yet, the possible impact of CAs on Ig and FLC subtypes and their levels is poorly studied in MM. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.The hypothesis is that CAs are associated with the involved Ig isotypes in MM. We carried out a systematic analysis of Ig and FLC subtypes and their serum levels in relation with common CAs using data on 523 patients recruited in German-Speaking Myeloma Multicenter Group (GMMG)-MM5 trial. 9, 10 For purpose of replication, an independent cohort of 325 cases from GMMG-HD4 trial was obtained. 11, 12Blood samples were collected prior to treatment initiation in the above trials, coordinated by ). The difference remained consistent, but smaller and of borderline significant in the GMMG-HD4 cohort (44.9 g/l vs 39.1 g/l; p=0.06).The individual FLCκ levels were outside the reference range for 80% of cases, and for 63% cases exceeded upper limit (>19.4 mg/l; Online Supplementary Table S4). FLCλ levels were outside the reference range for 63% cases, and for 31% cases surpassed upper limit (>26.3 mg/l). OnlineSupplementary In a previous study, higher rFLC was found in patients with t(14;16) or del(13). 5 We identified a significant suppression of rFLC in cases with gain 1q21 for IgG MM. M-protein levels in IgG MM were higher compared with those in IgA MM cases. This might be expected as IgG is the principal isotype in the blood and extracellular fluid whereas IgA is the principal isotype in secretions of mucus epithelium of the intestinal and respiratory tracts. The observation that M-protein levels were higher in any IgH translocation group compared with the hyperdiploidy group can possibly be attributed to the active production of M-protein in actively proliferating plasma cells driven by the translocated cyclin D genes. 15 Patients lacking hyperdiploidy had higher M-protein level compared with hyperdiploidy patients, although this difference was statistically significant for IgA MM alone.In summary, our study provides strong evidence for a complex modifying role of at least two CA types on immunophenotype. We showed further that serum Ig and FLC levels were influenced by several CA types. Our study thus sheds new light on the role of CA a...

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Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial

Cited by 64 publications

References 22 publications

Therapy for Relapsed Multiple Myeloma

Therapy for Relapsed Multiple Myeloma

Peripheral neuropathy associated with subcutaneous or intravenous bortezomib in patients with newly diagnosed myeloma treated within the GMMG MM5 phase III trial

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels

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