Myelosuppression Associated With Novel Therapies in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board

Miceli, Teresa; Colson, Kathleen; Gavino, Maria; Lilleby, K

doi:10.1188/08.cjon.s1.13-19

Cited by 18 publications

(18 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When combined with other therapeutic anticancer agents, BTZ could achieve even better clinical efficacy, thus leading to a full US FDA approval in 2005 as a second-line MM therapy [187,188], and as a first-line therapy for patients with newly diagnosed MM after only three years [189].Unfortunately, the therapeutic window of BTZ is relatively narrow and toxic side effects gradually started to appear, ranging from peripheral neuropathy, myelosuppression and cardiotoxicity. This is probably due to the accumulation of misfolded proteins in normal tissues [190][191][192]. Additionally, there is a relatively high incidence of developing an acquired resistance during treatment with BTZ.…”

Section: Bortezomib: First-in-class Proteasome Inhibitormentioning

confidence: 99%

Drug Development Targeting the Ubiquitin–Proteasome System (UPS) for the Treatment of Human Cancers

Zhang

Linder

Bazzaro

2020

Cancers

View full text Add to dashboard Cite

Cancer cells are characterized by a higher rate of protein turnover and greater demand for protein homeostasis compared to normal cells. In this scenario, the ubiquitin-proteasome system (UPS), which is responsible for the degradation of over 80% of cellular proteins within mammalian cells, becomes vital to cancer cells, making the UPS a critical target for the discovery of novel cancer therapeutics. This review systematically categorizes all current reported small molecule inhibitors of the various essential components of the UPS, including ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), ubiquitin ligases (E3s), the 20S proteasome catalytic core particle (20S CP) and the 19S proteasome regulatory particles (19S RP), as well as their mechanism/s of action and limitations. We also discuss the immunoproteasome which is considered as a prospective therapeutic target of the next generation of proteasome inhibitors in cancer therapies.Cancers 2020, 12, 902 2 of 34 core component of the nucleosome, which is critical for transcription and cell cycle, is recognized and linked by Lysine Residue 48 (K48) and further degraded by the proteasome [17,18]; DbpB (also named Y-box protein 1), a transcription factor, is reported to selectively recognize the Y-box promoter element. Studies showed that its terminal 105-amino-acid-long fragment is removed after a specific proteolytic cleavage by the proteasome complex [19,20]; NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is located outside the nucleus and is reported to be involved in DNA transcription as well as cell survival [21,22]. The NF-κB p105 is the precursor of NF-κB p50. It is evident that NF-κB p105 is cleaved and selectively degraded at the C-terminus by proteasome, generating the active form of NF-κB p50 [23]. Products of UPS degradation can also be further degraded into single amino acids by aminopeptidases [24]. Aminopeptidases are the class of enzymes that catalyze the final steps in the ubiquitin-proteasome pathway by breaking down shorter peptides (<5 residues) into even smaller fragments [25]. Many, but not all, of aminopeptidases, are zinc metalloenzymes, such as leucine aminopeptidases (lAPs) and methionine aminopeptidases (metAPs) [26,27]. Studies showed that blocking the activity of the aminopeptidases by inhibitor of bestatin could generate a major accumulation of peptides which are ∼2-5 residues long [28].The 26S proteasome contains one/two 19S regulatory particles (19S RP) which mainly regulate the translocation of ubiquitinated proteins to the 20S CP and one 20S core particle (20S CP) in which proteolysis finally occurs [29,30]. In general, two main processes are associated with the process of degradation of proteins by the UPS: (1) tagging the to-be-degraded proteins by polyubiquitination (normally more than four ubiquitins), and (2) proteolytic degradation of the polyubiquitinated protein by the 26S proteasome complex [31,32]. Each step incorporates an intricate and complex spectrum of protein interaction...

show abstract

Section: Bortezomib: First-in-class Proteasome Inhibitormentioning

confidence: 99%

Drug Development Targeting the Ubiquitin–Proteasome System (UPS) for the Treatment of Human Cancers

Zhang

Linder

Bazzaro

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Given the nature of MM and the agents used in its treatment, haematological toxicities are common complications (Zuckerman, 1998;Armoiry et al, 2008;Lonial et al, 2008;Miceli et al, 2008;Chen et al, 2009); melphalan is associated with myelosuppression http://emc.medicines.org.uk/medicine/4429/SPC/ Alkeran+Injection+50+mg., accessed December 2010), and bortezomib has been associated with transient, cyclical thrombocytopenia and neutropenia (Lonial et al, 2005(Lonial et al, , 2008. Therefore, haematological toxicities, including thrombocytopenia, neutropenia, anaemia, leucopenia and lymphopenia were frequent in the VISTA trial.…”

Section: Discussionmentioning

confidence: 99%

Characterization of haematological parameters with bortezomib–melphalan–prednisone versus melphalan–prednisone in newly diagnosed myeloma, with evaluation of long‐term outcomes and risk of thromboembolic events with use of erythropoiesis‐stimulating agents: analysis of the VISTA trial

et al. 2011

View full text Add to dashboard Cite

SummaryAlthough haematological toxicities, such as anaemia, are common in multiple myeloma (MM), no clear consensus exists on the use and impact of erythropoiesis-stimulating agents (ESA) on outcomes in MM. This analysis characterizes haematological toxicities and associated interventions in the phase III VISTA (Velcade Ò as Initial Standard Therapy in Multiple Myeloma:Assessment with Melphalan and Prednisone) study of bortezomib plus melphalan/prednisone (VMP, n = 344) versus MP (n = 338) in previously untreated MM patients ineligible for high-dose therapy, and evaluates the impact of ESA use or red-blood-cell (RBC) transfusions on outcomes and thromboembolic risk. Incidence of haematological toxicities was similar with VMP and MP; similar rates of interventions and associated complications (e.g. bleeding, febrile neutropenia) were observed. Two hundred thirty three patients received ESA; 204 had RBC transfusions. Frequency of thromboembolic events was low and not affected by ESA use. Median time-to progression (TTP) was similar between ESA/non-ESA [hazard ratio: 1AE03 (95% confidence interval 0AE76-1AE39); P = 0AE8478] in both arms (VMP: 19AE9/not reached; MP: 15AE0/17AE5 months). Three-year overall survival (OS) rates were similar between ESA/non-ESA in each arm. Patients receiving RBC transfusions had significantly shorter OS (P < 0AE0001) versus non-RBCtransfusion patients. In conclusion, bortezomib did not add to melphalan haematological toxicity. Concomitant ESA use with VMP/MP in previously untreated MM patients did not adversely affect TTP or OS, or increase thromboembolic risk. However, RBC transfusion was associated with significantly shorter survival.

show abstract

“…Although prophylaxis against Pneumocystis carinii pneumonia and fungal infections is accepted practice, antiviral prophylaxis is controversial (Zitella et al, 2006). Recommendations in the context of neutropenia are discussed in the Nurse Leadership Board's consensus statement on myelosuppression (Miceli et al, 2008).…”

Section: Immune System Signs and Symptomsmentioning

confidence: 99%

Steroid-Associated Side Effects in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board

Faiman

Bilotti²,

Mangan³

et al. 2008

Clinical Journal of Oncology Nursing

View full text Add to dashboard Cite

Steroids have been the foundation of multiple myeloma therapy for more than 30 years and continue to be prescribed as single agents and in combination with other antimyeloma drugs, including novel therapies. Steroids cause a wide range of side effects that affect almost every system of the body. Identification and prompt management of the toxicities contribute to the success of steroid-containing antimyeloma regimens. By following patients carefully and educating them and their caregivers, nurses can promote adherence to therapy and improve quality of life. The International Myeloma Foundation's Nurse Leadership Board developed this consensus statement for the management of steroid-associated side effects to be used by healthcare providers in any medical setting.

show abstract

Myelosuppression Associated With Novel Therapies in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board

Cited by 18 publications

References 13 publications

Drug Development Targeting the Ubiquitin–Proteasome System (UPS) for the Treatment of Human Cancers

Drug Development Targeting the Ubiquitin–Proteasome System (UPS) for the Treatment of Human Cancers

Characterization of haematological parameters with bortezomib–melphalan–prednisone versus melphalan–prednisone in newly diagnosed myeloma, with evaluation of long‐term outcomes and risk of thromboembolic events with use of erythropoiesis‐stimulating agents: analysis of the VISTA trial

Steroid-Associated Side Effects in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board

Contact Info

Product

Resources

About