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Multiple myeloma (also known as myelomatosis or myeloma) is a cancer in which there is abnormal growth in the number of plasma cells in the bone-marrow and blood. This can suppress the normal production of blood cells, including those associated with the body's immune system. The plasma cells may collect in the bone to make small tumours known as plasmacytomas. Multiple myeloma is most common in people aged over 60, and is rare before the age of 40.

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  • PubMed search for publications about Multiple Myeloma - Limit search to: [Reviews]

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    MeSH term: Multiple Myeloma
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Imataki O, Uemura M
Fatal Rhabdomyolysis Caused by Morganella morganii in a Patient with Multiple Myeloma.
Intern Med. 2017; 56(3):369-371 [PubMed] Related Publications
A 64-year-old Japanese man with multiple myeloma was admitted to our institute due to fever and hypotension. He had received multiple courses of chemotherapy just before his febrile episode. Blood culturing detected Morganella morganii. At the time of the diagnosis, his laboratory findings revealed massive rhabdomyolysis with a significantly increased creatinine kinase level (CK; 3,582 U/L); 98.8% of which corresponded to the CK-MB isotype. We diagnosed the patient with sepsis caused by M. morganii, complicated with severe rhabdomyolysis. He died of multi-organ failure 2 days later. Clinicians should closely observe patients with possible systemic infection-associated rhabdomyolysis.

Kosari F, Saffar H, Aghaei S
Cutaneous Involvement in Plasma Cell Myeloma: Report of a Case.
Acta Med Iran. 2016; 54(12):817-819 [PubMed] Related Publications
Plasma cellmyeloma constitutes about 10% of all hematologic malignancies. Metastatic cutaneous lesions without underlying bony involvement are rare and associated with advanced disease, poor prognosis and high tumor burden. IgG is the most common subtype and IgD is believed to have a more aggressive course.

Conticello C, Parisi M, Romano A, et al.
Pomalidomide experience: an effective therapeutic approach with immunomodulatory drugs in a patient with relapsed-refractory multiple myeloma.
Future Oncol. 2017; 13(5s):3-6 [PubMed] Related Publications
Here we discuss the case of a heavily pretreated male patient with relapsed-refractory multiple myeloma and previous monoclonal gammopathy of undetermined significance who initiated a fifth-line treatment with pomalidomide (4 mg orally, days 1-21 of a 28-day cycle) and low-dose dexamethasone (40 mg weekly orally). A total of 3 months later, very good partial response was achieved and complete response was maintained for 7 months. This case illustrates the field-practice experience on the benefits of pomalidomide in a relapsed-refractory multiple myeloma patient with a previous history of monoclonal gammopathy of undetermined significance. Indeed, the pomalidomide/dexamethasone regimen resulted in a longer progression-free survival compared with previous regimens and demonstrated a good long-term tolerability.

Palmas A, Piras G, Uras A, et al.
Pomalidomide in heavily pretreated refractory multiple myeloma: a case report.
Future Oncol. 2017; 13(5s):7-9 [PubMed] Related Publications
We present the case of a 70-year-old man diagnosed with multiple myeloma in 2008, who after four therapy lines initiated a fifth-line treatment with pomalidomide (4 mg orally, days 1-21 of a 28-day cycle) and low-dose dexamethasone (40 mg weekly orally). The patient was treated with pomalidomide for almost 2 years achieving a complete remission after 12 cycles. Complete remission was maintained for 9 months. This case illustrates the potential of pomalidomide plus low-dose dexamethasone to overcome multiple myeloma refractoriness inducing a quick and very prolonged remission.

Anitha D, Thomas B, Jan KS, Subburaj K
Risk of vertebral compression fractures in multiple myeloma patients: A finite-element study.
Medicine (Baltimore). 2017; 96(2):e5825 [PubMed] Free Access to Full Article Related Publications
The purpose of this study was to develop and validate a finite element (FE) model to predict vertebral bone strength in vitro using multidetector computed tomography (MDCT) images in multiple myeloma (MM) patients, to serve as a complementing tool to assess fracture risk. In addition, it also aims to differentiate MM patients with and without vertebral compression fractures (VCFs) by performing FE analysis on vertebra segments (T1-L5) obtained from in vivo routine MDCT imaging scans. MDCT-based FE models were developed from the in vitro vertebrae samples and were then applied to the in vivo vertebrae segments of MM patients (n = 4) after validation. Predicted fracture load using FE models correlated significantly with experimentally measured failure load (r = 0.85, P < 0.001). Interestingly, an erratic behavior was observed in patients with fractures (n = 2) and a more gradual change in FE-predicted strength values in patients without fractures (n = 2). Severe geometric deformations were also observed in models that have already attained fractures. Since BMD is not a reliable parameter for fracture risk prediction in MM subjects, it is necessary to use advanced tools such as FE analysis to predict individual fracture risk. If peaks are observed between adjacent segments in an MM patient, it can be safe to conclude that the spine is experiencing regions of structural instability. Such an FE visualization may have therapeutic consequences to prevent MM associated vertebral fractures.

Jimenez-Zepeda VH, Duggan P, Neri P, et al.
Bortezomib-containing regimens (BCR) for the treatment of non-transplant eligible multiple myeloma.
Ann Hematol. 2017; 96(3):431-439 [PubMed] Related Publications
In multiple myeloma (MM) patients ineligible for transplant, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor with anti-myeloma effects, have been reported. We aimed to evaluate the impact of different bortezomib-containing regimens (BCR) for the treatment of transplant-ineligible MM. All- consecutive patients treated with BCR at our institution from 01/05 to 02/16 were evaluated. With a median of 6 cycles, an overall response rate of 95.2, 80.9, and 76.3% was observed for patients treated with cyclophosphamide-bortezomib-dexamethasone (CyBorD), bortezomib-melphalan-prednisone (VMP), and bortezomib-dexamethasone (VD), respectively (p = 0.03). The median overall survival was similar between the three different BCR, but a trend for better progression-free survival was noted in favor of CyBorD. BCR are efficacious in the treatment of transplant-ineligible MM. Patients receiving continuous therapy (CT) exhibited better outcomes, suggesting that strategies to prevent toxicity and increase the cumulative dose are warranted.

Zuo W, Zhu X, Yang J, et al.
Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma: A case report.
Medicine (Baltimore). 2017; 96(1):e5787 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers.
CASE SUMMARY: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra. The patient was diagnosed with MM upon examination. A chest computed tomography (CT) scan revealed a round mass in the left lower lobe of the lungs, and a CT-guided needle biopsy uncovered a moderately differentiated adenocarcinoma. There were no additional notable findings in the left lung using positron emission tomography computed tomography (PET-CT). Therefore, a diagnosis of MM with pulmonary adenocarcinoma was made. Surgery was performed to excise the lung cancer. Bortezomib was used as first-line induction therapy against both tumors and lenalidomide was used for maintenance. The patient went into complete remission. Using this combined chemotherapy, the patient has survived for over 3 years since a diagnosis was made despite relapsing twice after the first year.
CONCLUSION: This report clearly delineates the diagnosis and treatment of a rare case of synchronous MM and pulmonary adenocarcinoma, as well as depicts a potentially positive outcome for the patient. It also overviews some diagnostic and therapeutic implications for clinicians.

Cohen YC, Zuckerman T, Yeshurun M, et al.
Efficacy and safety of autologous hematopoietic cell transplantation in elderly patients with multiple myeloma: a retrospective national multi-site cohort study.
Ann Hematol. 2017; 96(2):271-278 [PubMed] Related Publications
We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60-64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m(2) was more frequent in the 60-64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3-4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60-64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60-64.

Liu J, Li J, Chen M, Kuang L
Bortezomib followed by autologous stem cell transplantation in a patient with rheumatoid arthritis: A case report and review of the literature.
Medicine (Baltimore). 2016; 95(52):e5760 [PubMed] Free Access to Full Article Related Publications
RATIONALE AND PATIENTS CONCERNS: Despite the introduction of varied disease-modifying antirheumatic drugs and biological agents, a substantial proportion of patients remain untreatable. We report a 56-year-old Chinese female patient with a case of refractory rheumatoid arthritis (RA) complicated with multiple myeloma (MM) who was treated successfully with Bortezomib followed by autologous stem cell transplantation (ASCT).
DIAGNOSIS AND INTERVENTIONS: We report a 56-year-old Chinese female patient who was diagnosed as RA complicating with MM. She received 4 cycles of Bortezomib-based chemotherapy followed by ASCT. The response of her RA and MM were evaluated after every cycle of Bortezomib-based chemotherapy.
INTERVENTIONS AND OUTCOMES: After the first Bortezomib-based chemotherapy cycle, this patient's symptoms were significantly alleviated and thereafter the RA activity continued to improve. After the 4 courses of Bortezomib-based chemotherapy, the C-reactive protein was <0.5 mg/dL and the disease activity score 28-erythrocyte sedimentation rate was 2.0. No hematological or nonhematological side effects were observed during the treatment of Bortezomib.
LESSONS: Bortezomib might be a new safe and promising drug for refractory RA patients.

Himelstein AL, Foster JC, Khatcheressian JL, et al.
Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial.
JAMA. 2017; 317(1):48-58 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
Importance: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.
Objective: To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.
Design, Setting, Participants: Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.
Interventions: Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.
Main Outcomes and Measures: The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).
Results: Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ∞]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.
Conclusions and Relevance: Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.
Trial Registration: clinicaltrials.gov Identifier: NCT00869206.

Benyamini N, Avivi I, Dann EJ, et al.
Comparison of engraftment following different stem cell mobilization modalities in patients with multiple myeloma treated with a uniform induction regimen containing bortezomib, cyclophosphamide and dexamethasone.
Ann Hematol. 2017; 96(3):461-467 [PubMed] Related Publications
Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 10(6)/kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen.

Nel I, Thiolières JM, Ghillani-Dalbin P, et al.
Unexpected migration of free light chains in urinary protein electrophoresis.
Ann Biol Clin (Paris). 2017; 75(1):75-82 [PubMed] Related Publications
Urinary protein electrophoresis analysis (UPE) is an essential investigation for the study of abnormal proteins in urines. The interpretation of this analysis must be comprehensive and relevant. Indeed, UPE is often requested by clinicians and may have an important impact in patient's management. This paper presents two cases with free light chains showing unexpected electrophoretic migration which can lead to the misinterpretation of results. This article helps biologists to keep in mind the interest of UPE among the several analyses useful in the laboratory.

Berenson A, Vardanyan S, David M, et al.
Outcomes of multiple myeloma patients receiving bortezomib, lenalidomide, and carfilzomib.
Ann Hematol. 2017; 96(3):449-459 [PubMed] Related Publications
New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited. We have analyzed data from 258 MM patients who have received treatment with at least one of three agents: bortezomib, carfilzomib, and lenalidomide in a single clinic specializing in MM with respect to their responses and other outcomes to treatment regimens including these agents. Response rates were similar between these three drugs when used for the first time and again during subsequent treatment regimens. As expected, the clinical benefit rates (CBRs) were better for patients receiving their first treatment when compared to their use in subsequent treatment regimens. The CBRs were similar during their 2nd, 3rd, and 4th treatments containing these agents. Many patients refractory to these agents showed responses to regimens containing these same drugs when used in different combinations. In addition, patients refractory to one PI often responded to the other PI. The results of this study demonstrate that novel agents can be used repeatedly in novel combinations with significant clinical benefit for patients with MM.

Caldarella C, Annunziata S, Pagano L, et al.
Improved Detection of Minimal Residual Disease by 11C-Methionine PET/CT in a Young Patient With Unusual Extramedullary Presentation of Recurrent Multiple Myeloma.
Clin Nucl Med. 2017; 42(2):e130-e134 [PubMed] Related Publications
Extramedullary relapse of multiple myeloma (MM) is uncommon. A 40-year-old woman with history of MM underwent PET/CT using C-methionine (C-MET) after the detection of a vulvar lesion on MRI, biopsy proven to be extramedullary relapse of MM. The vulvar lesion was negative at the F-FDG PET/CT but showed high uptake of C-MET; focal uptake of both F-FDG and C-MET was shown within the muscles of the left leg, histologically confirmed as extramedullary relapse of MM. F-FDG PET/CT performed after chemotherapy showed no uptake in both sites, whereas posttreatment C-MET PET/CT showed persistence of residual uptake within the vulvar lesion.

Oiwa K, Morita M, Kishi S, et al.
High Risk of Tumor Lysis Syndrome in Symptomatic Patients with Multiple Myeloma with Renal Dysfunction Treated with Bortezomib.
Anticancer Res. 2016; 36(12):6655-6662 [PubMed] Related Publications
BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy.
PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated.
RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases).
CONCLUSION: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.

Berenson A, Vardanyan S, David M, et al.
Improved clinical outcomes for multiple myeloma patients treated at a single specialty clinic.
Ann Hematol. 2017; 96(3):441-448 [PubMed] Related Publications
Despite recent advances made in its treatment, multiple myeloma (MM) remains an incurable B cell malignancy. Thus, the objective for treating these patients is to prolong overall survival (OS) and preserve patients' quality of life. We have analyzed data from 264 consecutive MM patients who had their initial visit between July 1, 2004 and December 1, 2014 and have received treatment in a single clinic specializing in MM. We determined their progression-free survival (PFS, OS, and 5-year OS). The PFS for frontline (n = 165 treatments), salvage (n = 980), and all treatments (n = 1145) were 13.9, 4.6, and 5.5 months, respectively. The median OS of all patients was 98 months with a 5-year survival of 74%. The results of this study show a marked improvement in OS for unselected MM patients compared with historical data. There were no significant differences in OS between patients with different International Staging System (ISS) stages. Younger patients (<65 years old) showed a longer OS. The results of this study should help physicians predict outcomes for MM patients and be encouraging for patients with this B cell malignancy.

Xia C, Ribeiro M, Scott S, Lonial S
Daratumumab: monoclonal antibody therapy to treat multiple myeloma.
Drugs Today (Barc). 2016; 52(10):551-560 [PubMed] Related Publications
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed. Given the encouraging efficacy and acceptable safety profile, daratumumab has emerged as a novel treatment option for MM both as a monotherapy and in combination with conventional and novel anti-MM agents. This review will focus on preclinical pharmacology, pharmacokinetics, safety and clinical development of daratumumab in MM.

Offidani M, Corvatta L, Bringhen S, et al.
Salvage therapy in first relapse: a retrospective study in a large patient population with multiple myeloma.
Eur J Haematol. 2017; 98(3):289-295 [PubMed] Related Publications
OBJECTIVE: There is no strong evidence to guide therapeutic approach to multiple myeloma (MM) patients who experience first relapse. The treatment choice can be difficult since currently all patients are exposed to novel agents as thalidomide, bortezomib and lenalidomide.
METHODS: In this retrospective analysis, we evaluated the best therapeutic sequence, the role of retreatment, and the most beneficial cutoff of first remission in order to choose retreatment, analyzing 476 patients relapsed after first-line therapy.
RESULTS: Bortezomib-based regimens upfront followed by lenalidomide-based regimens at first relapse resulted in significantly better second progression-free survival (2ndPFS), PFS2, and overall survival (OS) compared to the opposite sequence. Changing therapy resulted in significantly better 2ndPFS in the whole population, whereas PFS2 was significantly longer only in patients who underwent maintenance therapy. Moreover, until PFS1 was shorter than 27 months, changing therapy at first relapse significantly extended 2ndPFS and PFS2 compared to retreatment, whereas similar outcomes were observed between the two strategies, when PFS1 was longer than 27 months.
CONCLUSION: Lacking randomized trials, our study could help to choose the most appropriate therapy algorithm in patients with MM.

Malard F, Harousseau JL, Mohty M
Multiple myeloma treatment at relapse after autologous stem cell transplantation: A practical analysis.
Cancer Treat Rev. 2017; 52:41-47 [PubMed] Related Publications
Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse. Next generation PI (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes: monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some of these new agents are now approved for multiple myeloma treatment at relapse. However choosing the most appropriate treatment at relapse may be difficult. This review sum up the most important studies and provide evidence to choose the most relevant therapeutic strategy for relapse after ASCT, based on disease, patient and previous treatment related parameters.

Dmytriw AA, Talla K, Smith R
Percutaneous sacroplasty for the management of painful pathologic fracture in a multiple myeloma patient: Case report and review of the literature.
Neuroradiol J. 2017; 30(1):80-83 [PubMed] Related Publications
Percutaneous kyphoplasty has a well-established role in the treatment of pathologic fractures in patients with multiple myeloma. Despite this, there is a scarcity of literature surrounding its use and efficacy in the sacrum. We present a case of successful symptom resolution in a patient with painful sacral fracture following sacroplasty, and review the existing literature. An 81-year-man with multiple myeloma presented to the hematology/oncology clinic with a history of excruciating pain while seated. The impact of this pain on his quality of life subjectively was rated to be particularly high. Computed tomography of the sacrum confirmed the presence of pathologic fracture within the S1 and S2 vertebrae. Under fluoroscopic guidance, polymethyl methacrylate (PMMA) bone cement was injected via 11-gauge needles using an anterior-oblique approach. No immediate post-procedural complications occurred, such as foraminal extravasation or venous injection. The patient reported himself to be pain-free 1 day following the procedure, and this remains the case to date at 2 years of follow-up. Sacroplasty is technically feasible and can provide durable relief of symptoms in patients with painful pathologic fractures of the sacrum. It is likely underused and can offer tremendous benefit to myeloma patients.

Zhang L, Cao D, Tang L, et al.
A panel of circulating miRNAs as diagnostic biomarkers for screening multiple myeloma: a systematic review and meta-analysis.
Int J Lab Hematol. 2016; 38(6):589-599 [PubMed] Related Publications
Circulating microRNAs (miRNAs) have been proved to be effective diagnostic markers for multiple myeloma (MM). The meta-analysis was aimed to evaluate the diagnostic value of related miRNAs. Multiple databases (PubMed, Web of Science, EMBASE, Cochrane Library, CBM, and CNKI) were systematically searched for available studies up to March 2016. All data were analyzed with the help of software revman 5.3 and metadisc 1.4. The eligible articles' quality was estimated by QUADAS-2, and pooled parameters were acquired with the bivariate random-effects meta-analysis model. Subgroup analysis and meta-regression were conducted to explore the heterogeneity of studies included. After steps of screening, seven qualified literatures were selected. They consisted of 22 studies that included 486 newly diagnosed MM patients and 292 healthy controls. Summary receiver operating characteristic (SROC) analyses of all miRNAs showed an area under the curve (AUC) of 0.86 (95%CI, 0.82-0.91). Together with the AUC, the positive likelihood ratio-PLR 4.45 (95%CI, 3.28-6.04), negative likelihood ratio-NLR 0.29 (95%CI, 0.24-0.35), and diagnostic odds ratio-DOR 17.59 (95%CI, 11.26-27.4) confirmed that circulating miRNAs possessed relatively high diagnostic value in discriminating MM patients from healthy controls. For miRNAs combined together, miRNA-1308/miRNA-720 had the highest sensitivity 0.96 (95%CI, 0.79-1.00) and specificity 0.92 (95%CI 0.64-1.0). The subgroup and meta-regression analyses also showed that miRNAs profiling was the sole source of heterogeneity, and the diagnostic accuracy of combined miRNAs was 6.02 times higher than single one. Combined circulating miRNAs in serum or plasma may be highly effective biomarker for diagnosis of MM.

Body JJ, Terpos E, Tombal B, et al.
Bone health in the elderly cancer patient: A SIOG position paper.
Cancer Treat Rev. 2016; 51:46-53 [PubMed] Related Publications
More than a third of cancers are diagnosed in people over the age of 75. Androgen deprivation for prostate cancer and aromatase inhibitors in breast cancer accelerate age-related bone loss and increase fracture rates. BMD should be checked by dual energy X-ray absorptiometry at baseline and, dependent on risk, every 12-24months. Sufficient calcium, vitamin D and exercise are part of primary fracture prevention. Resistance exercise in particular may improve functional activity and bone density. In men at increased fracture risk and women with postmenopausal early breast cancer, antiresorptive treatment is warranted to reduce fracture rate and to increase overall survival in breast cancer. Bone metastases (BM) are common in breast and prostate cancer and lytic bone lesions typical of multiple myeloma. They can cause fractures, pain and spinal cord compression, require surgery or radiation for symptom relief, and lead to hypercalcaemia. Multidisciplinary working with patients and carers can improve quality of life for elderly patients with BM and mitigate the adverse consequences of therapy. Bisphosphonates and other osteoclast inhibitors such as denosumab reduce this morbidity, improve quality of life and reduce pain. Especially in the elderly, attention should be paid to renal function and to risk factors for osteonecrosis with bone-modifying agents. Attention should also be paid to hypocalcaemia risk, which can be considerable in elderly men with metastatic prostate cancer and vitamin D deficiency. We urgently need further research specifically directed at assessing risks and benefits of bone targeted treatments in the growing population of elderly cancer patients.

Badar T, Srour S, Bashir Q, et al.
Predictors of inferior clinical outcome in patients with standard-risk multiple myeloma.
Eur J Haematol. 2017; 98(3):263-268 [PubMed] Related Publications
INTRODUCTION: Outcome of patients with standard-risk (SR) multiple myeloma (MM) has improved; however, subsets of patients do worse than expected. We sought to identify the factors associated with inferior outcome.
METHODS: We evaluated 51 patients with SR MM that received upfront autologous hematopoietic stem cell transplantation (auto-HCT) after induction and had a progression-free survival (PFS) of ≤18 months.
RESULTS: The median age of patients was 61 yr. Forty-one (80%) patients received induction with immunomodulatory drugs, proteosome inhibitors, or combination of both. The overall response rate (ORR) after auto-HCT was 96% (stringent complete response 23%, complete response 10%, very good partial response 22%, and partial response 39%). The median PFS was 7.8, and median overall survival (OS) was 56.3 months. On univariate analysis, concurrent light-chain amyloidosis (AL) was associated with inferior PFS [hematological response (HR); 2.51, 95% CI; 0.64-10.58, P = 0.03] and occurrence of soft tissue plasmacytoma was associated with a significantly shorter OS (HR: 3.05, 95% CI: 0.57-16.29, P = 0.02).
CONCLUSION: Our analysis suggests that concurrent AL and soft tissue plasmacytoma were associated with shorter PFS and OS, respectively. Heterogeneity in clinical outcome of SR MM merits better tools for prognostication, such as gene expression profiling and minimal residual disease assessment to identify high-risk patients.

Zhu W, Chen W
Bortezomib-based treatment for multiple myeloma patients with renal impairment: A systematic review and meta-analysis of observational studies.
Medicine (Baltimore). 2016; 95(46):e5202 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
BACKGROUND: Renal insufficiency is a common and severe complication of patients with multiple myeloma. The aim of this study was to evaluate bortezomib-based treatment for multiple myeloma patients with renal insufficiency.
METHODS: The Cochrane Library, Embase, PubMed, ISI, China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Chongqing VIP Database, and Wan Fang Data were systematically searched to identify observational studies from January 1, 2001, to December 31, 2015. Myeloma response rate and renal remission rate were pooled by using risk ratio and 95% confidence interval (CI). The Cochran Q and I statistics were used to assess heterogeneity. Sensitivity analysis was performed to test the feasibility of pooled results. Publication bias was conducted when included studies were ≥9. Furthermore, grades of evidence were performed to evaluate study quality.
RESULTS: Eleven retrospective cohort studies were included in the final analysis. The number of available studies and risk ratios (95% CI) were, respectively, 10 and 1.48 (95% CI: 1.28-1.71) for myeloma overall response, 6 and 3.69 (95% CI: 2.22-6.13) for myeloma complete response, 9 and 1.47 (95% CI: 1.28-1.69) for renal overall remission, and 8 and 1.49 (95% CI: 1.26-1.75) for renal complete remission. No significant publication bias was observed and sensitivity analysis confirmed the stability of results. The overall qualities of evidence were high for myeloma complete response and medium for the other 3 outcomes based on the Grading of Recommendations, Assessment, Development and Evaluation system.
CONCLUSION: Current evidence indicated that bortezomib-based treatment could improve myeloma overall response (especially myeloma complete response) and renal overall remission (including renal complete remission).

van de Velde H, Londhe A, Ataman O, et al.
Association between complete response and outcomes in transplant-eligible myeloma patients in the era of novel agents.
Eur J Haematol. 2017; 98(3):269-279 [PubMed] Related Publications
OBJECTIVES: Achieving complete response (CR) has been linked to improved progression-free (PFS) and overall (OS) survival in myeloma. A meta-analysis was conducted to investigate whether this holds true in the era of novel agents (bortezomib, lenalidomide, thalidomide).
METHODS: A total of 24 studies in newly diagnosed patients undergoing autologous stem cell transplantation (ASCT) that reported associations between responses and long-term outcomes (PFS/OS rates post-ASCT by response, or hazard ratios with 95% confidence intervals from Cox models) were identified and analyzed.
RESULTS: Achievement of CR vs. CONCLUSIONS: Achieving CR during first-line therapy remains important in the novel-agent era; magnitude of association between achieving CR and outcomes appears higher for CR obtained using novel vs. non-novel agents.

Jin Z, Zhou S, Zhang Y, et al.
Lycorine induces cell death in MM by suppressing Janus Kinase/signal transducer and activator of transcription via inducing the expression of SOCS1.
Biomed Pharmacother. 2016; 84:1645-1653 [PubMed] Related Publications
Despite the use of novel anti-myeloma agents,nearly all patients will eventually relapse or become refractory to drug treatment. New and more effective drugs for multiple myeloma (MM) are urgently needed. The JAK-STAT signaling pathway is important in the proliferation of myeloma cells.Lycorine,a natural alkaloid extracted from amaryllidaceae, has shown anti-tumor effects against a variety of solid tumors. However, its effects on MM remain unclear.In this study,we found that lycorine inhibited cellular viability and induced cell death in MM cell lines and primary myeloma cells which were derived from our four MM patients. The study showed that myeloma cells' cycle was being arrested under the G0/G1 phase followed by the lycorine treatment. Further mechanism analysis demonstrated that lycorine inhibited JAK2/STAT signaling through upregulation of SOCS1 in MM cells and patient MM cells.Importantly, we found that knockdown of HDAC8 resulted in increased expression of SOCS1. Collectively, our findings suggested lycorine acted as a potent novel histone deacetylase inhibitor and inhibited JAK2/STAT signaling through upregulation of SOCS1 in MM cells.

Asmar A, Simonsen L, Svolgaard B, Bülow J
Unexpected Diffuse 18F-NaF Uptake in the Lung Parenchyma in a Patient With Severe Hypercalcemia Due to Myelomatosis.
Clin Nucl Med. 2017; 42(1):68-69 [PubMed] Related Publications
An 84-year-old man was admitted to the intensive care unit because of hypercalcemic crisis leading to acute renal failure needing dialysis. The patient had no other history of illness. However, because prostate-specific antigen levels were increased, the patient was referred to F-NaF PET/CT on suspicion of active skeletal metastases. The patient was finally diagnosed with myelomatosis. Although the skeletal uptake of F-NaF was without signs of focal metastasis, the F-NaF PET/CT scanning surprisingly revealed diffuse high accumulation of F-NaF in the lung parenchyma, possibly because of calcium deposition in the lung parenchyma associated to amyloidosis seen in patients with myelomatosis.

Lang T, Nie Y
MiR-148a participates in the growth of RPMI8226 multiple myeloma cells by regulating CDKN1B.
Biomed Pharmacother. 2016; 84:1967-1971 [PubMed] Related Publications
OBJECTIVE: The aim of this study is to explore the influence of miR-148a on cell proliferation and cell cycle of multiple myeloma (MM) cell line RPMI8226 and the related molecular mechanism.
METHODS: The expression of miR-148a and CDKN1B in MM cells and primary cells of normal bone marrow were determined by RT-PCR and western blotting. The cell proliferation and cell cycle of miR-148a knockdown MM cells and normal MM cells were determined by flow cytometry. The protein expression of p-NPAT, p-Rb and p-CDC6 was determined in normal and miR-148a knockdown MM cells. Luciferase reported assay was used to explore the relationship between miR-148a and CDKN1B.
RESULTS: The level of miR-148a in MM cells was much higher than that in primary cells from healthy bone marrow samples, while the expression of CDKN1B was lower in MM cells. After knockdown of miR-148a, cell cycle mainly distributed at G0/G1 and the proliferation capacity of MM cells decreased. Knockdown of miR-148a significantly reduced protein expression of p-NPAT, p-Rb and p-CDC6. Luciferase reported assay showed that miR-148a could directly target CDKN1B at 3'-UTR.
CONCLUSIONS: High level of miR-148a inhibits CDK activity and promotes the proliferation of MM cells at least partly by downregulating CDKN1B.

Schabel C, Horger M, Kum S, et al.
Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography.
Eur J Radiol. 2016; 85(12):2195-2199 [PubMed] Related Publications
INTRODUCTION: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation.
OBJECTIVE: To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide.
MATERIALS AND METHODS: Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69±9.2years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2-4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Respmed) and response of all myeloma manifestations including osteolyses (Resptotal) was performed using the corrected contingency coefficient (Ccorr).
RESULTS: The correlation between Respmed based on length diameter and transverse diameter and Resptotal was perfect (Ccorr=1.0; p<0.0001) whereas the correlation based on density was moderate (Ccorr=0.54; p<0.0001). The evaluation of simplified response criteria with a measurement of only 2 medullary lesions yielded the best sensitivity and specificity valued for treatment-induced changes for the length diameter evaluation with 94.4%/95.7% for prediction of progressive disease and 78.6%/93.3% for prediction of therapy response. There were no significant differences between patients treated with bortezomib and lenalidomide (p>0.05).
CONCLUSION: Measurements of size of a minimum of two medullary lesions is sufficient for response assessment and correlates very well with the course of lytic bone lesions and that of hematologic parameters.

Ferraro RA, Ivanidze J, Margolskee E, et al.
Invasive granulomatous cryptococcal sinusitis in an adult with multiple myeloma.
Clin Imaging. 2017 Jan - Feb; 41:65-68 [PubMed] Related Publications
We report a case of cryptococcal sinusitis, a rare presentation of Cryptococcus neoformans infection in a patient with multiple myeloma. The objective of this case report is to highlight the utility of structural and functional imaging modalities in the differential diagnosis of sinonasal soft tissue masses in the immunocompromised patient population. PET-CT was the first imaging modality in this patient, who presented for routine follow-up staging of multiple myeloma, and was asymptomatic at the time of his presentation. PET-CT findings prompted further evaluation with MRI, to aid in the differential diagnosis with respect to a neoplastic versus infectious etiology. Ultimately, surgical excision with histopathology was required to provide definitive diagnosis. Final histopathology displayed yeast-organism staining consistent with Cryptococcus neoformans/gatti. The patient subsequently underwent treatment for this infection, along continued treatment for multiple myeloma. To our knowledge this is the first known case of cryptococcal sinusitis in a patient with neoplastic disease. Imaging represents an important tool to differentiate fungal infection from neoplasm in the immunocompromised patient population. As the population of immunocompromised patients continues to grow, the relevance of this diagnosis as well as the use of alternative imaging modalities is becoming more important in clinical practice.

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