scholarly journals Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma

2017 ◽  
Vol 7 (9) ◽  
pp. e600-e600 ◽  
Author(s):  
M Binder ◽  
S V Rajkumar ◽  
R P Ketterling ◽  
P T Greipp ◽  
A Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Newly Diagnosed ◽  
Chromosome 13 ◽  
Prognostic Implications

scholarly journals Prognostic Implications of Multiple Cytogenetic High-Risk Abnormalities in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5615-5615
Author(s):  
Moritz Binder ◽  
S. Vincent Rajkumar ◽  
Rhett P. Ketterling ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Cumulative Effect ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Kaplan Meier ◽  
Prognostic Implications

Abstract Background: Cytogenetic evaluation using fluorescence in situ hybridization (FISH) at the time of diagnosis is essential for initial risk stratification in multiple myeloma. The presence of specific cytogenetic abnormalities is known to confer a poor prognosis, less is known about the cumulative effect of multiple cytogenetic high-risk abnormalities. We aimed to evaluate the prognostic implications of the presence of multiple cytogenetic high-risk abnormalities at the time of diagnosis. Methods: We studied 226 patients who were diagnosed with multiple myeloma between July 2004 and July 2014 at Mayo Clinic Rochester, underwent FISH evaluation within six months of diagnosis, and presented with cytogenetic high-risk abnormalities. High-risk cytogenetics were defined as t(4;14), t(14;16), t(14;20), del(17p), or gain(1q). Bone marrow aspirates were evaluated for deletions, monosomies, trisomies, and tetrasomies using chromosome- or centromere-specific FISH probes. IGH rearrangements were evaluated using an IGH break-apart probe and evaluating up to five potential partners (FGFR3, CCND1, CCND3, MAF, and MAFB). Kaplan-Meier overall survival estimates were calculated and the log-rank test was used to compare overall survival in patients with single and multiple cytogenetic high-risk abnormalities. A multivariable-adjusted Cox regression model was used to assess the effect of multiple cytogenetic high-risk abnormalities on overall survival adjusting for age, sex, and Revised International Staging System (R-ISS) stage. P-values below 0.05 were considered statistically significant. Results: The median age at diagnosis was 65 years (32 - 90), 129 (57%) of the patients were male. The median overall survival was 3.5 years (3.1 - 4.9) for the entire cohort (n = 226), 4.0 years (3.3 - 5.1) for those with one cytogenetic high-risk abnormality (n = 182, 80%), and 2.6 years (1.7 - 3.1) for those with two cytogenetic high-risk abnormalities (n = 44, 20%). There were no patients with more than two cytogenetic high-risk abnormalities. Ninety-eight patients (45%) had a high-risk translocation, 77 (35%) had del(17p), 39 (18%) had a high-risk translocation plus del(17p), and 5 (2%) had gain(1q) plus either a high-risk translocation or del(17p). Figure 1 shows the Kaplan-Meier overall survival estimates stratified by the number of cytogenetic high-risk abnormalities (n = 226). The presence of two cytogenetic high-risk abnormalities (compared to one) was of prognostic significance after adjusting for age, sex, and R-ISS stage (HR 2.01, 95% CI 1.27 - 3.19, p = 0.003, n = 205). Conclusions: Approximately one in five patients with newly diagnosed high-risk multiple myeloma presented with two high-risk abnormalities at the time of diagnosis. These patients experienced inferior overall survival suggesting a cumulative effect of multiple cytogenetic high-risk abnormalities. The relatively low number of observed gain(1q) was likely related to the fact that not all patients were evaluated for that abnormality. Therefore the presented hazard ratio represents a conservative effect estimate and may underestimate the true effect. Figure 1 Figure 1. Disclosures Dispenzieri: GSK: Membership on an entity's Board of Directors or advisory committees; Jannsen: Research Funding; Alnylam: Research Funding; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; pfizer: Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding; Amgen: Research Funding. Kumar:Janssen: Consultancy, Research Funding; BMS: Consultancy; AbbVie: Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Array BioPharma: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Kesios: Consultancy; Glycomimetics: Consultancy.

Preliminary Report of Risk-Based Approach in Korean Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4911-4911 ◽  
Author(s):  
Soo-Mee Bang ◽  
Jae Hoon Lee ◽  
Sung-Soo Yoon ◽  
Seonyang Park ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Chromosome 13 ◽  
Beta 2 ◽  
The Impact

Abstract Purpose: The purpose of this study was to examine the impact of different approaches stratified on risk based on chromosome 13 deletion and serum beta-2 microglobulin (MG) level would lead to survival benefit in patients with newly-diagnosed multiple myeloma. Patients and Methods: At diagnosis, fresh marrow samples for FISH and serum for beta-2 MG were sent to central laboratory and reviewed. Patients who had chromosome 13 deletion and high beta-2 MG (>2.5 mg/L) were considered to have high-risk disease. Patients without chromosome 13 deletion and low beta-2 MG were classified as low-risk group. Intermediate-risk group had to have either one of these two risk factors. After VAD induction chemotherapy, autologous stem cell transplantation conditioned with MEL200 was performed in patients at high- and intermediate-risk. DECP consolidation chemotherapy was added for high-risk patients. Patients who achieved CR after VAD in low-risk did not receive any further treatment. Results: As of Jun 2004, 50 patients were registered from 10 centers. Median age was 58 (range, 39–68) years old. Chromosome 13 deletion was detected in 18 patients (36%) and beta-2 MG was elevated in 39 patients (78%). Thirteen patients were classified as high-risk, 31 patients as intermediate-risk and 6 patients as low-risk. After median follow-up of 9 months, progression-free and overall survival at 1-year were 56% and 76%, respectively. To date, no statistically significant differences in survival were observed between risk groups (figure 1). Conclusion: In this study, risk-based approach in patients with multiple myeloma appeared to be feasible. Study accrual is ongoing and updated results will be presented. Figure Figure

scholarly journals MUKnine OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e046225
Author(s):  
Sarah Brown ◽  
Debbie Sherratt ◽  
Samantha Hinsley ◽  
Louise Flanagan ◽  
Sadie Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Plasma Cell ◽  
Phase Ii ◽  
Whole Body ◽  
Cell Leukaemia ◽  
High Dose ◽  
Newly Diagnosed ◽  
Genetic Changes ◽  
Novel Treatment

IntroductionMultiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients.Methods and analysisThe Myeloma UK nine OPTIMUM trial (MUKnine) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUKnine a), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUKnine b) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUKnine b primary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing.Ethics and disseminationEthics approval London South East Research Ethics Committee (Ref: 17/LO/0022, 17/LO/0023). Results of studies will be submitted for publication in a peer-reviewed journal.Trial registration numberISRCTN16847817, May 2017; Pre-results.

Newly Diagnosed Multiple Myeloma is Associated with Hypercoagulability and High Risk of VTE The ROADMAP Study

2016 ◽  
Vol 16 ◽  
pp. S76-S77
Author(s):  
Despina Fotiou ◽  
Grigoris Gerotziafas ◽  
Flora Zagouri ◽  
Theodoros Sergentanis ◽  
Kimon Stamatelopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Newly Diagnosed

scholarly journals Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 3 (5) ◽  
pp. 744-750 ◽  
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
S. Vincent Rajkumar ◽  
Morie A. Gertz ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Light Chain ◽  
Progression Free Survival ◽  
Early Response ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Best Response ◽  
Light Chain Disease ◽  
The Impact

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and <VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P < .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

scholarly journals Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4250-4256 ◽  
Author(s):  
G Tricot ◽  
B Barlogie ◽  
S Jagannath ◽  
D Bracy ◽  
S Mattox ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Poor Prognosis ◽  
Chromosomal Abnormalities ◽  
Multivariate Regression Analysis ◽  
Significant Variable ◽  
Chromosome 13 ◽  
Reactive Protein ◽  
Dismal Prognosis ◽  
Prognostic Implications ◽  
Beta 2 Microglobulin

Chromosomal abnormalities have major biologic and prognostic implications in leukemias. Cytogenetic information in typically hypoproliferative multiple myeloma (MM) is limited because of difficulties in obtaining analyzable metaphases. In this study, karyotypes and other known prognostic factors were analyzed in 155 newly diagnosed MM patients, entered on an intensive treatment program with two autotransplants. Complete remission (CR), event-free (EFS) and overall survival (OS) were analyzed using standard statistical methods. Abnormal cytogenetics were found in 39% of patients and were associated with a significantly lower CR rate (27% v 48%; P = .008). EFS and OS were inferior in patients with either partial or complete deletion of chromosome 13 or 11q abnormalities (“unfavorable” karyotype) when compared with the remaining patients (P < .001) who, as a group, had a similar prognosis irrespective of cytogenetic findings, ie, inevaluable, normal, or abnormal but without an “unfavorable” karyotype. The patients with abnormalities of both chromosomes 11 and 13 had a dismal prognosis with median EFS and OS of only 11 and 12 months, respectively. Significant associations were noted between an “unfavorable” karyotype and IgA isotype, elevated levels of beta-2 microglobulin (B2M, > or = 3 mg/L) and age > 60 years. On multivariate regression analysis, the absence of an “unfavorable” karyotype was the most significant variable associated with prolonged EFS and OS (P = .0001 and .0002, respectively). Other independent favorable variables were age less than 60 years, C-reactive protein (CRP) < or = 0.4 mg/dL and bone marrow plasmacytosis < or = 50% before treatment. On a multivariate analysis without cytogenetics, these same three standard parameters were identified as the only favorable variables. Patients not having all three standard favorable variables had a significantly lower CR rate (P = .03), EFS (P = .0001), and OS (P = .002) if an unfavorable karyotype was detected. We conclude that, in this program of uniformly treated MM patients, a poor prognosis was associated predominantly with abnormalities of chromosomes 11 and 13.

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