Showing papers by "Mario Boccadoro published in 2014"
TL;DR: Consolidation therapy with high-dose melphalan plus stem-cell transplantation, as compared with MPR, significantly prolonged progression-free and overall survival among patients with multiple myeloma who were 65 years of age or younger.
Abstract: Background This open-label, randomized, phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan–prednisone–lenalidomide (MPR) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma. Methods We randomly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction, and 251 patients to lenalidomide maintenance therapy or no maintenance therapy. The primary end point was progression-free survival. Results The median follow-up period was 51.2 months. Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR (median progression-free survival, 43.0 months vs. 22.4 months; hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.32 to 0.61; P<0.001; and 4-year overall su...
623 citations
TL;DR: It is concluded that NGS is an effective tool for MRD monitoring in ALL, MCL and MM and showed at least the same level of sensitivity as allele-specific oligonucleotides-PCR, without the need for patient-specific reagents.
Abstract: In this study, we compared immunoglobulin heavy-chain-gene-based minimal residual disease (MRD) detection by real-time quantitative PCR (RQ-PCR) and next-generation sequencing (NGS) to assess whether NGS could overcome some limitations of RQ-PCR and further increase sensitivity, specificity, accuracy and reproducibility. In total, 378 samples from 55 patients with acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL) or multiple myeloma (MM) were investigated for clonotype identification, clonotype identity and comparability of MRD results. Forty-five clonotypes were identified by RQ-PCR and 49 by NGS. Clonotypes identified by both tools were identical or >97% homologous in 96% of cases. Both tools were able to routinely reach a sensitivity level of 1 × E-05. A good correlation of MRD results was observed (R=0.791, P<0.001), with excellent concordance in 79.6% of cases. Few discordant cases were observed across all disease subtypes. NGS showed at least the same level of sensitivity as allele-specific oligonucleotides-PCR, without the need for patient-specific reagents. We conclude that NGS is an effective tool for MRD monitoring in ALL, MCL and MM. Prospective comparative analysis of unselected cases is required to validate the clinical impact of NGS-based MRD assessment.
262 citations
University of Turin1, Mayo Clinic2, University of Arkansas for Medical Sciences3, Norwegian University of Science and Technology4, Erasmus University Rotterdam5, Sapienza University of Rome6, VU University Medical Center7, Monash University8, National and Kapodistrian University of Athens9, University of Ostrava10, University of Bologna11, Harvard University12, Roswell Park Cancer Institute13
TL;DR: Patients with newly diagnosed myeloma who received lenalidomide had an increased risk of developing haematological second primary malignancies, driven mainly by treatment strategies that included a combination of lenalidoide and oral melphalan.
Abstract: Summary Background Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure. Methods We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012, and in which at least one group received lenalidomide were eligible for inclusion. We obtained individual patient data (age, sex, date of diagnosis, allocated treatment and received treatment, duration of treatment and cause of discontinuation, maintenance treatment, date of first relapse, date of second primary malignancy diagnosis, type of second primary malignancy, date of death or last contact, and cause of death) by direct collaboration with the principal investigators of eligible trials. Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis. Findings We found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment (2620 had received lenalidomide and 598 had not), and were included in our analyses. Cumulative incidences of all second primary malignancies at 5 years were 6·9% (95% CI 5·3–8·5) in patients who received lenalidomide and 4·8% (2·0–7·6) in those who did not (hazard ratio [HR] 1·55 [95% CI 1·03–2·34]; p=0·037). Cumulative 5-year incidences of solid second primary malignancies were 3·8% (95% CI 2·7–4·9) in patients who received lenalidomide and 3·4% (1·6–5·2) in those that did not (HR 1·1 [95% CI 0·62–2·00]; p=0·72), and of haematological second primary malignancies were 3·1% (95% CI 1·9–4·3) and 1·4% (0·0–3·6), respectively (HR 3·8 [95% CI 1·15–12·62]; p=0·029). Exposure to lenalidomide plus oral melphalan significantly increased haematological second primary malignancy risk versus melphalan alone (HR 4·86 [95% CI 2·79–8·46]; p Interpretation Patients with newly diagnosed myeloma who received lenalidomide had an increased risk of developing haematological second primary malignancies, driven mainly by treatment strategies that included a combination of lenalidomide and oral melphalan. These results suggest that alternatives, such as cyclophosphamide or alkylating-free combinations, should be considered instead of oral melphalan in combination with lenalidomide for myeloma. Funding Celgene Corporation.
237 citations
San Antonio River Authority1, University of Turin2, University of Eastern Piedmont3, University of Catania4, Sapienza University of Rome5, University of Rome Tor Vergata6, University of Padua7, University of Milan8, Casa Sollievo della Sofferenza9, University of Bari10, Marche Polytechnic University11, University of Bologna12
TL;DR: Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation and were significantly more frequent in the VMPT-VT patients.
Abstract: Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The...
192 citations
TL;DR: Recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence are presented.
Abstract: Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B).
188 citations
TL;DR: Results showed high complete response rates and a good safety profile, and the most frequent grade 3 to 5 toxicities were neutropenia, anemia, and cardiopulmonary adverse events.
127 citations
Erasmus University Rotterdam1, The Royal Marsden NHS Foundation Trust2, University of Turin3, Katholieke Universiteit Leuven4, National and Kapodistrian University of Athens5, Heidelberg University6, Karolinska Institutet7, University of Southern Denmark8, University of Navarra9, University of Ostrava10, University of Giessen11
TL;DR: In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option, and Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency.
Abstract: The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results.
91 citations
TL;DR: Topical corticosteroid therapy for corneal toxicity from systemically administered cytarabine and the use of prophylactic eye drops during high-dose cytosine arabinoside therapy is recommended.
Abstract: 1 Patel AK, Sheehan W, Jenkins A, Lane C, Kell J. Prophylactic treatment for cytosine arabinoside-induced keratoconjunctivitis. Int Ophthalmol 2011; 31: 191–195. 2 Matteucci P, Carlo-Stella C, Di Nicola M, Magni M, Guidetti A, Marchesi M et al. Topical prophylaxis of conjunctivitis induced by high-dose cytosine arabinoside. Haematologica 2006; 91: 255–257. 3 Higa GM, Gockerman JP, Hunt AL, Jones MR, Horne BJ. The use of prophylactic eye drops during high-dose cytosine arabinoside therapy. Cancer 1991; 68: 1691–1693. 4 Watson SL, Coroneo MT. Steroids and the eye. Med Today 2001; 2: 79–85. 5 Nerkelun S, Kellermann S, Nenning H. [Acute blindness caused by fungal infection in chronic myeloid leukemia]. Klin Monatsbl fur Augenheilkunde 1997; 211: 272–274. 6 Gressel MG, Tomsak RL. Keratitis from high doses intravenous cytarabine. Lancet 1982; 2: 273. 7 Lass JH, Lazarus HM, Reed MD, Herzig RH. Topical corticosteroid therapy for corneal toxicity from systemically administered cytarabine. Am J Ophthalmol 1982; 94: 617–621. 8 Elliott GA, Schut AL. Studies with cytarabine HCl (CA) in normal eyes of man, monkey and rabbit. Am J Ophthalmol 1965; 60: 1074–1082. 9 Kaufman HE, Capella JA, Maloney ED, Robbins JE, Cooper GM, Uotila MH. Corneal toxicity of cytosine arabinoside. Arch Ophthalmol 1964; 72: 535–540.
77 citations
TL;DR: Multiple myeloma is a hematologic tumor characterized by accumulation of monoclonal plasma cells in the bone marrow producing antigen-specific immunoglobulins and the transcription factor X box binding protein 1 (XBP1), the interferon regulatory factor 4 (IRF4), the transcriptional
Abstract: Multiple myeloma (MM) is a hematologic tumor characterized by accumulation of monoclonal plasma cells (PCs) in the bone marrow (BM) producing antigen-specific immunoglobulins. The transcription factor X box binding protein 1 (XBP1), the interferon regulatory factor 4 (IRF4) and the transcriptional
45 citations
TL;DR: Exclusive or predominant use of once-weekly bortezomib dosing in GIMEMA once- weekly and GEM2005MAS65 resulted in high efficacy, comparable with that demonstrated in VISTA, and similar cumulative bortzomib dose with reduced toxicity.
Abstract: Substantial efficacy has been demonstrated with bortezomib-melphalan-prednisone in phase III studies in transplant-ineligible myeloma patients using various twice-weekly and once-weekly bortezomib dosing schedules. In VISTA, the regimen comprised four 6-week twice-weekly cycles, plus five 6-week once-weekly cycles. In the GIMEMA MM-03-05 study, the bortezomib-melphalan-prednisone regimen was either per VISTA (‘GIMEMA twice-weekly’), or comprised nine 5-week once-weekly cycles (‘GIMEMA once-weekly’). In the GEM2005MAS65 study, the regimen comprised one 6-week twice-weekly cycle, plus five 5-week once-weekly cycles. We evaluated the cumulative bortezomib dose administered during bortezomib-melphalan-prednisone, as well as efficacy and tolerability, using patient-level study data. Over all bortezomib-melphalan-prednisone cycles (nine in VISTA/GIMEMA; six in GEM2005MAS65), the median cumulative bortezomib dose administered was 38.5, 42.1, 40.3, and 32.9 mg/m2 in VISTA, GIMEMA twice-weekly, GIMEMA once-weekly, and GEM2005MAS65, respectively, and the respective proportions of planned bortezomib dose actually delivered were 57.0%, 62.3%, 86.1%, and 90.4%. Response rates following bortezomib-melphalan-prednisone were 74–87% and appeared generally similar between studies. Three-year survival rates were 67.9–75.7% across studies. Grade 3/4 peripheral neuropathy rates were 13% in VISTA and 14% in GIMEMA twice-weekly, but were lower at 2% in GIMEMA once-weekly and 7% in GEM2005MAS65. Discontinuations and bortezomib dose reductions due to peripheral neuropathy were reduced in GIMEMA once-weekly versus VISTA and GIMEMA twice-weekly. Exclusive or predominant use of once-weekly bortezomib dosing in GIMEMA once-weekly and GEM2005MAS65 resulted in high efficacy, comparable with that demonstrated in VISTA, and similar cumulative bortezomib dose with reduced toxicity. Trials are registered with ClinicalTrials.gov: VISTA (Identifier:00111319), GIMEMA MM-03-05 (Identifier:01063179), and GEM2005MAS65 (Identifier:00443235).
44 citations
TL;DR: The present results suggest that the strategy of maintenance therapy might improve the outcome of poor-risk AML/MDS patients and reduce minimal residual disease in five of eight evaluable patients.
Abstract: We evaluated a maintenance, post-remission treatment with low-dose chemotherapy plus differentiating agents on poor-prognosis acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients ineligible to allografting. Patients had either age over 60 and/or secondary AML, therapy-related AML, previous relapse, high-risk MDS. Forty-five patients received the maintenance therapy based on two alternated schedules: (a) 6-thioguanine + 13-cis retinoic acid + dihydroxylated vitamin D3 and (b) low-dose cytarabine + 6-mercaptopurine + all-trans retinoic acid + dihydroxylated vitamin D3. We compared their outcome, at a median follow-up of 52 months, to that of a matched population of 49 patients who stopped treatments after consolidation. Maintenance group had a lower relapse incidence (70.3 vs. 86.4 % at 5 years p = 0.007) and a longer disease-free survival (median 21.2 vs. 8.7 months, p = 0.017). The relapse reduction improved overall survival: median 40.4 months (35.9 % at 5 years) for maintenance group vs. 15.8 (14.2 % at 5 years) for controls (p = 0.005). At multivariate Cox analysis, both cytogenetic and maintenance therapies resulted independent outcome predictors for overall survival. Maintenance treatment also reduced minimal residual disease (detected by WT1 and CBFβ-MYH11) in five of eight evaluable patients. The present results suggest that our strategy of maintenance therapy might improve the outcome of poor-risk AML/MDS patients.
TL;DR: The results indicate that regulatory T cells may not be the main players of immunological tolerance to myeloma cells under base-line conditions, but their fully preserved immune competence may promote their inadvertent activation and blunt T-cell driven anti-myeloma immune interventions even after myel cancer cells have successfully been cleared by chemotherapy.
Abstract: Conflicting data have been reported about the frequency and function of regulatory T cells in multiple myeloma. Most studies have investigated peripheral blood rather than bone marrow Tregs and side-by-side comparisons with bone marrow from healthy donors have still not been made. In this study, we show that regulatory T-cells total count, subset distribution, and expression of chemokine receptors are similar in the bone marrow of myeloma patients and healthy donors. Regulatory T cells are not recruited by myeloma cells in the bone marrow and their counts are unaffected by the tumor burden and the disease status. The diversity of T-cell receptor repertoire is highly preserved ensuring broad reactivity and effective suppressor function. Our results indicate that regulatory T cells may not be the main players of immunological tolerance to myeloma cells under base-line conditions, but their fully preserved immune competence may promote their inadvertent activation and blunt T-cell driven anti-myeloma immune interventions even after myeloma cells have successfully been cleared by chemotherapy.
TL;DR: Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS in patients who received VMP in comparison with those treated with MPT.
Abstract: Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2-microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients (P = 0.007). After a median follow-up of 34 months (range, 1-92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52-0.82; P < 0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32-0.59; P < 0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients ≥ 75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control-case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT.
TL;DR: High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high β2‐microglobulin further characterizes patients with worse outcome.
Abstract: Abnormal activation of MET/HGF (Hepatocyte Growth Factor) pathway has been described in several tumours and increased HGF plasmatic levels have been detected in patients with aggressive multiple myeloma (MM). MET and HGF mRNA expression was investigated in 105 samples of purified plasma cells derived from newly diagnosed MM patients treated with bortezomib-based induction therapy. Gene expression was compared with response to therapy and clinical outcome. MET gene copy number was also evaluated. MET mRNA expression was higher in CD138(+) than in CD138(-) cells (median 76·90 vs. 11·24; P = 0·0009). Low MET mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56·10 vs. 134·83; P = 0·0006). After a median follow-up of 50 months, patients with high MET mRNA expression displayed a worse progression-free survival (PFS; P = 0·0029) and overall survival (OS; P = 0·0023) compared to those with low MET mRNA levels. Patients with both high MET mRNA expression and high β2-microglobulin level (>5·5 mg/l) had further worse median PFS (P < 0·0001) and OS (P < 0·0001). Patients carrying 4 MET gene copies (8 out of 82, 9·8%) also had a short PFS. High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high β2-microglobulin further characterizes patients with worse outcome.
TL;DR: A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19+/CD117− immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma.
Abstract: Multiple myeloma is a plasma cell disorder characterized by malignant plasma cell infiltration in the bone marrow, serum and/or urine monoclonal protein and organ damage. The aim of this study was to investigate the impact of chromosome 1 abnormalities in a group of elderly patients (>65 years) with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-03-05 trial and treated with bortezomib, melphalan and prednisone or bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance. We also evaluated the link between chromosome 1 abnormalities and other clinical, genetic and immunophenotypic features by a multivariate logistic regression model. Interphase fluorescence in situ hybridization on immunomagnetically purified plasma cells and bone marrow multiparameter flow cytometry were employed. A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19+/CD117− immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma. Moreover, a detrimental effect of thalidomide, even when administered in association with bortezomib, was observed in patients with abnormal chromosome 1 as well as in those with 17p deletion, while the benefit of adding thalidomide to the bortezomib-melphalan-prednisone regimen was noted in patients carrying an aggressive CD19+/CD117− bone marrow plasma cell immunophenotype. This trial was registered at www.clinicaltri-als.gov as #NCT01063179.
Journal Article•
TL;DR: This is the first report, to the authors' knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.
Abstract: We present a case of Trichoderma fungemia with pulmonary involvement in a multiple myeloma patient, who was severely immunocompromised and heavily treated with high-dose melphalan, and underwent autologous hematopoietic cell transplantation. This is the first report, to our knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.
TL;DR: Evaluating depth of response by molecular methods induced by graft-vs-myeloma following tandem autologous/non-myeloablative allografting in newly diagnosed myeloma found that those who reached nested PCR negativity showed molecular relapse two years before clinical relapse and 1 relapsed 8 months after the last PCR-negative sample.
TL;DR: Evaluated PFS1, PFS2 and OS in newly diagnosed multiple myeloma (NDMM) patients who received CT or FDT, finding that continuous therapy significantly prolongs remission duration and resistant relapse may reduce the duration of subsequent remission.
Abstract: 8515 Background: Continuous therapy significantly prolongs remission duration, resistant relapse may reduce the duration of subsequent remission which can negatively impact on OS. PFS1 defines the ...
TL;DR: This Phase I/II study was designed to determine the maximum tolerated dose (MTD) of once weekly carfilzomib combined with cyclophosphamide-dexamethasone (wCCd) and to assess safety and efficacy of this combination in elderly patients with newly diagnosed MM.
TL;DR: The clinical utility of cf-DNA in the monitoring of minimal residual disease (MRD) of pts with multiple myeloma carrying the tumor specific immunoglobulin (IGH) rearrangement is investigated.
DOI•
01 Jan 2014TL;DR: The goal of many recent studies aims at evaluating individual patients and their overall risk of progression, the detection of early signs of progression and the development of timely treatment strategies.
Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a non malignant plasma cell disorder with a relatively low risk of progression to Multiple Myeloma (MM) and to related Plasma cells disordes (lymphoplasmacellular neoplasms, Waldenstrom Macroglobulinemia or light chain amyloidosis). It is a quite common finding, especially in the population above the age of 50 and it can also present in association with many non malignant conditions. Differential diagnosis of symptomatic and asymptomatic forms is the determinant for starting therapy. Over the last few years many advances in the understanding of the biology of MGUS, together with large epidemiological studies, allowed to define risk models to estimate the risk of progression to MM according to MGUS isotype and, more recently, to peculiar flow cytometry findings. The goal of many recent studies aims at evaluating individual patients and their overall risk of progression, the detection of early signs of progression and the development of timely treatment strategies.
TL;DR: In NDMM patients, Mel200-ASCT significantly improved PFS and OS in comparison with CC+R, and these data suggest intensifying treatment in good-prognosis patients and in patients with a chemo-sensitive disease.
TL;DR: This trial compared Rd vs. MPR vs. CPR in newly diagnosed multiple myeloma patients ≥65 years old in a multicenter phase III trial and found no difference in PFS and overall survival (OS) was observed.
TL;DR: Evaluated the incidence of SPMs in newly diagnosed MM patients enrolled in the GIMEMA 26866138-MMY-3006 multicentre phase III study and suggest that treatment with PI might decrease the risk of developing a SPM compared to IMiDs based treatment.
TL;DR: Palumbo et al. as mentioned in this paper found that miR-130a was decreased in serum samples of patients developing extramedullary (EM) disease and distinguished EM pts from newly diagnosed multiple myeloma (MM) patients with specificity over 90%.
TL;DR: Lower MRD values, both with MFC and RQ-PCR procedures, predict better outcome suggesting that MRD levels can be modified by maintenance.