scholarly journals Effective dose and size-specific dose estimate (ssde) of the torso In low dose mdct protocol in multiple myeloma

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Lyra M ◽  
Rouchota M ◽  
Michalitsi M ◽  
Boultadaki A ◽  
Letsas B ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Effective Dose ◽  
Low Dose ◽  
Dose Estimate

Effective dose estimate and implementation of the size-specific dose estimate index in multiple myeloma patients examined by low dose MDCT Protocol

2014 ◽  
Vol 30 ◽  
pp. e58-e59
Author(s):  
M. Michalitsi ◽  
A. Boultadaki ◽  
J. Floros ◽  
M. Rouchota ◽  
M. Argyrou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Effective Dose ◽  
Low Dose ◽  
Dose Estimate

scholarly journals Whole Body Low Dose Computed Tomography Using Third-Generation Dual-Source Multidetector With Spectral Shaping: Protocol Optimization and Literature Review

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097313
Author(s):  
Dario Baldi ◽  
Liberatore Tramontano ◽  
Vincenzo Alfano ◽  
Bruna Punzo ◽  
Carlo Cavaliere ◽  
...  
Keyword(s):  
Effective Dose ◽  
Low Dose ◽  
Whole Body ◽  
Dose Length Product ◽  
Osteolytic Lesions ◽  
Subjective Image Quality ◽  
Ct Dose ◽  
Dual Source ◽  
Ct Dose Index ◽  
Low Dose Computed Tomography

For decades, the main imaging tool for multiple myeloma (MM) patient’s management has been the conventional skeleton survey. In 2014 international myeloma working group defined the advantages of the whole-body low dose computed tomography (WBLDCT) as a gold standard, among imaging modalities, for bone disease assessment and subsequently implemented this technique in the MM diagnostic workflow. The aim of this study is to investigate, in a group of 30 patients with a new diagnosis of MM, the radiation dose (CT dose index, dose-length product, effective dose), the subjective image quality score and osseous/extra-osseous findings rate with a modified WBLDCT protocol. Spectral shaping and third-generation dual-source multidetector CT scanner was used for the assessment of osteolytic lesions due to MM, and the dose exposure was compared with the literature findings reported until 2020. Mean radiation dose parameters were reported as follows: CT dose index 0.3 ± 0.1 mGy, Dose-Length Product 52.0 ± 22.5 mGy*cm, effective dose 0.44 ± 0.19 mSv. Subjective image quality was good/excellent in all subjects. 11/30 patients showed osteolytic lesions, with a percentage of extra-osseous findings detected in 9/30 patients. Our data confirmed the advantages of WBLDCT in the diagnosis of patients with MM, reporting an effective dose for our protocol as the lowest among previous literature findings.

Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2458-2466 ◽  
Author(s):  
Dharminder Chauhan ◽  
Guilan Li ◽  
Klaus Podar ◽  
Teru Hideshima ◽  
Constantine Mitsiades ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Exposure ◽  
Low Dose ◽  
Benzodiazepine Receptors ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Superoxide Generation ◽  
Insulin Growth Factor ◽  
Bortezomib Treatment ◽  
Induced Apoptosis

Abstract Bortezomib (PS-341), a selective inhibitor of proteasomes, induces apoptosis in multiple myeloma (MM) cells; however, prolonged drug exposure may result in cumulative toxicity and the development of chemoresistance. Here we show that combining PK-11195 (PK), an antagonist to mitochondrial peripheral benzodiazepine receptors (PBRs), with bortezomib triggers synergistic anti-MM activity even in doxorubicin-, melphalan-, thalidomide-, dexamethasone-, and bortezomib-resistant MM cells. No significant cytotoxicity was noted in normal lymphocytes. Low-dose combined PK and bortezomib treatment overcomes the growth, survival, and drug resistance conferred by interleukin-6 or insulin growth factor within the MM bone marrow milieu. The mechanism of PK + bortezomib–induced apoptosis includes: loss of mitochondrial membrane potential; superoxide generation; release of mitochondrial proteins cytochrome-c (cyto-c) and Smac; and activation of caspases-8/-9/-3. Furthermore, PK + bortezomib activates c-Jun NH2 terminal kinase (JNK), which translocates to mitochondria, thereby facilitating release of cyto-c and Smac from mitochondria to cytosol. Blocking JNK, by either dominant-negative mutant (DN-JNK) or cotreatment with a specific JNK inhibitor SP600125, abrogates both PK + bortezomib–induced release of cyto-c/Smac and induction of apoptosis. Together, these preclinical studies suggest that combining bortezomib with PK may enhance its clinical efficacy, reduce attendant toxicity, and overcome conventional and bortezomib resistance in patients with relapsed refractory MM.

Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography

2005 ◽  
Vol 54 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Marius Horger ◽  
Claus D. Claussen ◽  
Ulrike Bross-Bach ◽  
Reinhard Vonthein ◽  
Tobias Trabold ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Conventional Radiography ◽  
Whole Body ◽  
Multidetector Row Ct ◽  
Multidetector Row

Phase I Study of 30-Minute Infusion of Carfilzomib As Single Agent or in Combination With Low-Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

2015 ◽  
Vol 33 (7) ◽  
pp. 732-739 ◽  
Author(s):  
Kyriakos P. Papadopoulos ◽  
David S. Siegel ◽  
David H. Vesole ◽  
Peter Lee ◽  
Steven T. Rosen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Concentration ◽  
Phase I ◽  
Phase I Study ◽  
Low Dose ◽  
Single Agent ◽  
Phase Iii ◽  
Maximum Plasma ◽  
Irreversible Inhibitor ◽  
Refractory Multiple Myeloma

Purpose Carfilzomib is an irreversible inhibitor of the constitutive proteasome and immunoproteasome. This phase I study evaluated the maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carfilzomib administered as a 30-minute intravenous (IV) infusion. Safety and efficacy of carfilzomib as a single agent or in combination with low-dose dexamethasone were assessed. Patients and Methods Patients with relapsed and/or refractory multiple myeloma (MM) were administered single-agent carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Cycle one day 1 and 2 doses were 20 mg/m2, followed thereafter by dose escalation to 36, 45, 56, or 70 mg/m2. Additionally, carfilzomib was combined with low-dose dexamethasone (40 mg/wk). Results Thirty-three patients were treated with single-agent carfilzomib. Dose-limiting toxicities in two patients at 70 mg/m2 were renal tubular necrosis and proteinuria (both grade 3). The MTD was 56 mg/m2. Nausea (51.5%), fatigue (51.5%), pyrexia (42.4%), and dyspnea and thrombocytopenia (each 39.4%) were the most common treatment-related toxicities. Overall response rate (ORR) was 50% (56-mg/m2 cohort). Increasing carfilzomib dosing from 20 to 56 mg/m2 resulted in higher area under the plasma concentration-time curve from time zero to last sampling and maximum plasma concentration exposure with short half-life (range, 0.837 to 1.21 hours) and dose-dependent inhibition of proteasome chymotrypsin-like activity. In 22 patients treated with 45 or 56 mg/m2 of carfilzomib plus low-dose dexamethasone, the ORR was 55% with a safety profile comparable to that of single-agent carfilzomib. Conclusion Carfilzomib administered as a 30-minute IV infusion at 56 mg/m2 (as single agent or with low-dose dexamethasone) was generally well tolerated and highly active in patients with relapsed and/or refractory MM. These data have provided the basis for the phase III randomized, multicenter trial ENDEAVOR.

scholarly journals A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma

Cancer ◽  
2017 ◽  
Vol 123 (23) ◽  
pp. 4617-4630 ◽  
Author(s):  
Jatin J. Shah ◽  
Jonathan L. Kaufman ◽  
Jeffrey A. Zonder ◽  
Adam D. Cohen ◽  
William I. Bensinger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Phase 1 ◽  
Refractory Multiple Myeloma

scholarly journals Three Drug Regimens for Newly Diagnosed Multiple Myeloma Transplant-Ineligible Elderly Patients - a Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5574-5574
Author(s):  
Abdul Aziz Siddiqui ◽  
Kazi Najamus-saqib Khan ◽  
Arafat Ali Farooqui ◽  
Muhammad Saad Farooqi ◽  
Muhammad Junaid Tariq ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Trial ◽  
Alkylating Agents ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Great Efficacy ◽  
Drug Regimens

Introduction: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) tend to have comorbidities and/or advanced age that make this subset of patients difficult to manage with current drug regimens. Methods: A comprehensive literature search of PubMed, Embase, Clinicaltrials.gov and Web of Science was performed from inception and completed on 07/17/2019. Studies focusing on efficacy and tolerability of 3-drug regimens in patients with NDMM were included for the review. Results: Out of 3579 studies, a total of 10 (08 phase II and 03 phase III) clinical trials in last ten years (2010-2019) using 3-drug regimens in NDMM elderly pts (893M/807F) ineligible for ASCT (determined by investigators) were selected. A total of 1703/1740 NDMM pts were evaluated. Proteasome inhibitors (PIs) such as carfilzomib (C), bortezomib (V) and ixazomib (I) showed promising results in elderly transplant-ineligible NDMM pts. CLARION trial (phase III, n=955) compared two PIs (C and V) with melphalan (M) and prednisone. There was no statistically significant difference in progression-free survival (PFS) between two groups (median: 22.3 vs 22.1 months; HR: 0.91; 95% CI, 0.75-1.10, p = 0.159) as well as overall survival (OS) (HR: 1.08; 95% CI: 0.82-1.43). Difference in the least square means of the HR-QoL (Health related- quality of life) was 4.99 (p<.0001) favoring C-group. M may not be an ideal drug to combine with carfilzomib in this setting given more AEs.(Facon et al 2019). V as 3-drug regimen in combination with lenalidomide (L) in 242 pts achieved statistically significant prolonged PFS (median 43 mo) and OS (median 75 mo) with great efficacy and acceptable risk-benefit profile. (Durie et al 2017; phase III). Multinational phase II trial (n=70) by Dimopoulos et al (2019) evaluated I, with different fixed doses of cyclophosphamide (Cy). Median duration was 19 cycles, indicating the long-term tolerability of regimen. With favorable toxicity profile and maintained QoL scores, trial concluded that this therapy is tolerable in elderly transplant-ineligible NDMM pts. Tuchman et al (2017) in phase II trial (n=14) investigated (V-Cy-d) and achieved ORR of 64%, with ≥VGPR of 57%. Low dose V showed great efficacy with M yielding ORR of 86% and VGPR or better of 49% in phase II trial (n=101) that also evaluated Cy as 3-drug combination but results were more productive with M with longer PFS and OS which reduced when impact of frailty was examined on outcomes. Since toxicity was higher with M, trial suggested that 2-drug combination should be preferred in elderly frail patients. (Larocca et al 2015). Efficacy was quite promising when Bringhen et al (2014) trialed C with Cy-d; 87% OS and 76% PFS at 1 y in phase II trial (n=58) with much favorable safety profile. Monoclonal antibodies (mAb) such as elotuzumab (E) and pembrolizumab (Pe) are also tested in elderly. First study conducted on NDMM pts using humanized mAb; E, in phase II trial (n=40) by Takezako et al (2017) attained primary endpoint of the study (ORR) of (88%) and VGPR or better of 45% in Japanese pts with tolerable toxicities in elderly. No subjects on this study experienced severe peripheral neuropathy. KEYNOTE-185; a phase III multinational trial by Usmani et al (2019) evaluated Pe with Ld in 151 pts. FDA halted this study due to unfavorable benefit-risk profile; 19 deaths, 6 due to disease progression (PD), and 13 due to treatment-related AEs. Median PFS and median OS were not reached in either group. Immunomodulators such as L achieved one of the longest PFS reported in a trial of transplant ineligible patients (35 mo) by using LVd regimen in phase II multicenter trial (n=50). (O'Donnell et al 2018) Alkylating agents like bendamustine (ben) and M have been tested in different novel regimens. Decreasing intensity and increasing duration of ben resulted in better outcomes in phase II trial (n=59) by Berdeja et al (2016) and can be given as first line treatment. Ben yielded great results with low dose dexa as compared to high dose achieving 92% ORR. Original regimen was effective but relatively more toxic. Incidence of herpes and neuropathy decreased dramatically with the treatment modifications. Conclusion: Three-drug regimens having PIs, mABs, immunomodulators and alkylating agents have shown desirable results in NDMM transplant (ASCT)-ineligible elderly patients and are likely the emerging standard of care for NDMM. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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