Early versus late treatment for smoldering (asymptomatic) multiple myeloma: A systematic review.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8593-8593
Author(s):  
Mubarak Salem Alahamdi ◽  
Jason Tay
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
High Risk ◽  
Disease Progression ◽  
Controlled Trial ◽  
Population Sample ◽  
Expectant Management ◽  
Therapeutic Interventions ◽  
Current Standard ◽  
Risk Of Disease

8593 Background: Expectant management remains the current standard of care for patients with smoldering multiple myeloma (SMM). Recent appreciation of "high risk" smoldering myeloma and the advent of novel therapeutic agents may allow one to better tailor the timing of therapeutic interventions. Herein, we performed a systematic review of the literature, summarizing the available randomized controlled trial (RCT) evidence for treatment of SMM. Methods: Our systematic search strategy includes MEDLINE, EMBASE, Cochrane Database, and relevant bibliographies where the following search concepts were used: RCT, SMM as defined as per the IMW Criteria, and treatment. Two reviewers independently extracted data on study design, population, sample size, treatment, clinical outcomes, and trial quality, were any discrepancies were discussed and resolved. Results: We identified 7 RCTs (2 articles and 5 abstracts) representing 869 patients. Six articles compared early versus deferred treatment for SMM; 2 studies compared early Melphalan plus Prednisone (MP) versus deferred MP. 3 studies compared bisphosphonates versus abstention while one study compared lenalidomide with dexamethasone to therapeutic abstention. Further, one study compared thalidomide with zoledronate to zoledronate alone. The median age is 66. Four studies received a Jadad score of 3 while three studies received a score of 2. Allocation concealment was described in four studies. Risk of disease progression was lower in patients receiving therapy compared to abstention OR 0.5(0.38-0.68). The events that demonstrate disease progression were not clearly defined. Further, the use of combination therapy compared to a single intervention decreased the risk of progression OR 0.23(0.11-0.51). No difference in OS was noted in patients receiving therapy compared to abstention OR 0.95(0.57-1.57). Conclusions: Early treatment of SMM compared with abstention decreases the risk of disease progression. However, OS was not improved by earlier intervention. High risk SMM may benefit from early intervention. The optimal intervention(s) remains to be defined, and further studies are warranted in this understudied population.

Smoldering Multiple Myeloma: When to Observe and When to Treat?

2015 ◽  
pp. e484-e492 ◽  
Author(s):  
María-Victoria Mateos ◽  
Jesús-F San Miguel
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Correct Diagnosis ◽  
Standard Of Care ◽  
Current Standard ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Risk Of Disease ◽  
Definition Of

Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of at least 3 g/dL of serum M-protein and/or 10% to 60% bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to active multiple myeloma (MM) is not uniform and several markers are useful for identifying patients at high risk of progression. The definition of the disease has recently been revisited and patients with asymptomatic MM at 80% to 90% of progression risk at 2 years are now considered to have MM. Although the current standard of care is not to treat, a randomized trial in patients with high-risk SMM that compared early treatment versus observation demonstrated that early intervention resulted in substantial benefits in terms of time to progression and overall survival (OS). These findings highlight the need to follow a correct diagnosis by an accurate risk stratification to plan an optimized follow-up according to the risk of disease progression.

scholarly journals Genomic profiling of smoldering multiple myeloma identifies patients at a high risk of disease progression.

2019 ◽  
Vol 19 (10) ◽  
pp. e5-e6 ◽  
Author(s):  
Mark Bustoros ◽  
Romanos Sklavenitis-Pistofidis ◽  
Jihye Park ◽  
Robert Redd ◽  
Binyamin Zhitomirsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Disease Progression ◽  
Genomic Profiling ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Disease

scholarly journals Phase II Trial of the Combination of Ixazomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 804-804 ◽  
Author(s):  
Mark Bustoros ◽  
Chia-jen Liu ◽  
Kaitlen Reyes ◽  
Kalvis Hornburg ◽  
Kathleen Guimond ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Risk ◽  
Disease Progression ◽  
Board Of Directors ◽  
Rna Sequencing ◽  
Research Funding ◽  
Response Rate ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background. This study aimed to determine the progression-free survival and response rate using early therapeutic intervention in patients with high-risk smoldering multiple myeloma (SMM) using the combination of ixazomib, lenalidomide, and dexamethasone. Methods. Patients enrolled on study met eligibility for high-risk SMM based on the newly defined criteria proposed by Rajkumar et al., Blood 2014. The treatment plan was designed to be administered on an outpatient basis where patients receive 9 cycles of induction therapy of ixazomib (4mg) at days 1, 8, and 15, in combination with lenalidomide (25mg) at days 1-21 and Dexamethasone at days 1, 8, 15, and 22. This induction phase is followed by ixazomib (4mg) and lenalidomide (15mg) maintenance for another 15 cycles. A treatment cycle is defined as 28 consecutive days, and therapy is administered for a total of 24 cycles total. Bone marrow samples from all patients were obtained before starting therapy for baseline assessment, whole exome sequencing (WES), and RNA sequencing of plasma and bone marrow microenvironment cells. Moreover, blood samples were obtained at screening and before each cycle to isolate cell-free DNA (cfDNA) and circulating tumor cells (CTCs). Stem cell collection is planned for all eligible patients. Results. In total, 26 of the planned 56 patients were enrolled in this study from February 2017 to April 2018. The median age of the patients enrolled was 63 years (range, 41 to 73) with 12 males (46.2%). Interphase fluorescence in situ hybridization (iFISH) was successful in 18 patients. High-risk cytogenetics (defined as the presence of t(4;14), 17p deletion, and 1q gain) were found in 11 patients (61.1%). The median number of cycles completed was 8 cycles (3-15). The most common toxicities were fatigue (69.6%), followed by rash (56.5%), and neutropenia (56.5%). The most common grade 3 adverse events were hypophosphatemia (13%), leukopenia (13%), and neutropenia (8.7%). One patient had grade 4 neutropenia during treatment. Additionally, grade 4 hyperglycemia occurred in another patient. As of this abstract date, the overall response rate (partial response or better) in participants who had at least 3 cycles of treatment was 89% (23/26), with 5 Complete Responses (CR, 19.2%), 9 very good partial responses (VGPR, 34.6%), 9 partial responses (34.6%), and 3 Minimal Responses (MR, 11.5%). None of the patients have shown progression to overt MM to date. Correlative studies including WES of plasma cells and single-cell RNA sequencing of the bone microenvironment cells are ongoing to identify the genomic and transcriptomic predictors for the differential response to therapy as well as for disease evolution. Furthermore, we are analyzing the cfDNA and CTCs of the patients at different time points to investigate their use in monitoring minimal residual disease and disease progression. Conclusion. The combination of ixazomib, lenalidomide, and dexamethasone is an effective and well-tolerated intervention in high-risk smoldering myeloma. The high response rate, convenient schedule with minimal toxicity observed to date are promising in this patient population at high risk of progression to symptomatic disease. Further studies and longer follow up for disease progression are warranted. Disclosures Bustoros: Dava Oncology: Honoraria. Munshi:OncoPep: Other: Board of director. Anderson:C4 Therapeutics: Equity Ownership; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Takeda Millennium: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Oncopep: Equity Ownership. Richardson:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ghobrial:Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy; BMS: Consultancy.

Impact of anti-CD38 therapy in multiple myeloma with high-risk cytogenetics: systematic review and meta-analysis

2020 ◽  
Vol 61 (10) ◽  
pp. 2519-2522
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Monia Sigle ◽  
Viveksandeep Thoguluva Chandrasekar ◽  
Muhammad Aziz ◽  
Al-Ola Abdallah ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
High Risk ◽  
Meta Analysis

scholarly journals Validation of a national algorithm for diabetes screening

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
G Lavranos ◽  
C Chrysostomou ◽  
M Leonidou ◽  
M Prodromou
Keyword(s):  
High Risk ◽  
Clinical Laboratory ◽  
Population Sample ◽  
World Health ◽  
Diabetic Patients ◽  
Second Phase ◽  
Diabetes Diagnosis ◽  
Diabetes Screening ◽  
Current Standard ◽  
The World

Abstract Background The continuing upward trend in diabetes diagnosis across the world has led governments to adopt new treatment programs. According to the International Federation for Diabetes (2017) Europe and in its Member States spent from 10% to 20% of healthcare costs, for diabetes. The purpose of this study is to assess the feasibility of an algorithm to identify both the regulatory needs of diabetic individuals and to screen for undiagnosed individuals in the community. Methods The population sample consisted of 2100 people. The survey was conducted in two phases over the period 2017-2018. In the first phase we identified the 188 already diagnosed people with diabetes who were asked to answer a questionnaire comparing their current standard of care to NICE indicators. In the second phase, the remaining 1912 non-diabetic patients were asked to answer the Findrisk questionnaire. Those who were classified as high risk and very high risk were selected and referred to a clinical laboratory where they were subjected to a glucose curve to detect any diagnosis. Results The diabetes prevalence at the onset of the study was 9% (188/2100 people). Fifty-two new incidents were diagnosed. Thirty-six new cases were diagnosed by randomized glucose values after triple check and symptomatic diabetes symptoms consistent with the World Health Organization’s recommendations on diabetes diagnosis. Sixteen new cases were diagnosed via OGTT. The prevalence of diabetes at the end of the survey reached 11.4% (240/2,100 people).. Conclusions It has been found that one person in every forty in the general population suffers from diabetes without been yet diagnosed. Deviations from international diabetes standards have been observed. A new diabetes strategy should be implemented in the future, allowing the catholic implementation of the Findrisk Diabetes Prevention tool every ten years. Key messages Despite existing guidelines and recommendations, very few diabetic patients fulfill NICE follow up criteria. FINDRISK and OGTT can be used as part of a cost-effective national diabetes screening algorithm.

scholarly journals Evaluation of Functional and Cytogenetic High-Risk Multiple Myeloma Using Real-World Data

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4093-4093
Author(s):  
Ankit Kansagra ◽  
Eric Hansen ◽  
Andrew J. Belli ◽  
Stefanie Goran ◽  
Ching-Kun Wang
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Disease Progression ◽  
Real World ◽  
Multivariate Analyses ◽  
Rapid Disease Progression ◽  
High Risk Patients ◽  
Risk Patients ◽  
High Risk Populations ◽  
Equity Ownership

Abstract Introduction: Multiple myeloma (MM) is a heterogeneous disease with wide variability in outcomes. The presence of cytogenetic abnormalities in MM is of critical importance for prognosis and risk stratification. However, patients who may or may not have sufficient cytogenetic abnormalities to classify as high-risk can still experience rapid disease progression despite therapy, or functional high risk (FHR) disease. These two high risk cohorts comprise vulnerable subpopulations who have a significant burden of disease, and it is critical that we understand the underlying patient characteristics and optimal treatment sequence. We sought to investigate these two high risk patient populations treated in the contemporary real-world practice setting. Methods: A total of 1719 patients were identified in the COTA real-world database as having been diagnosed with active MM on or after January 1, 2015 and classified as either FHR, cytogenetic high risk (CHR), or both. The COTA real-world database is a USA-based real-world evidence database comprised of longitudinal, Health Insurance Portability and Accountability Act (HIPAA)-compliant, data on the diagnosis, clinical management, and outcomes of patients with cancer. Of the 1719 patients, 1260 were identified to be FHR, defined as relapse <18 months from initial active MM diagnosis. A total of 459 patients were identified as CHR, among which 347 were both FHR and CHR. CHR was defined as a patient having at least one of the following abnormalities: t(4;14), t(14;16), t(14;20), del(17p), 1q gain, or hypoploid. Line of therapy was applied programmatically using an algorithm based on International Myeloma Working Group criteria and clinical guidance. The primary outcome was time to next treatment (TTNT) calculated using the Kaplain Meier method. Univariate and multivariate analyses were conducted to understand predictors of rapid disease progression among high-risk patients. Results: In our real-world population, FHR patients tended to be slightly younger, African American, and treated predominantly in the academic setting (Table 1). First-line (1L) and second-line (2L) treatment patterns by category are shown in Table 2. A lower proportion of FHR patients received 1L immunomodulators as compared to the other high-risk groups, while almost half of the CHR patients received 1L stem cell transplant (SCT). In 2L, among patients not receiving 2L SCT, a higher proportion of CHR patients received a daratumamab-based treatment as compared to FHR (23.2% vs. 12.0%, respectively). We observed a longer median (95% CI) TTNT for high-risk patients receiving 2L daratumamab-based treatment as compared to patients who did not: 8.5 months (6.4-13.0) vs. 6.0 months (5.3-6.9), p=0.07 (Figure 1). Univariate and multivariate analyses showed age at diagnosis (HR: 0.98, CI: 0.97, 0.99), normal cytogenetics (HR: 0.78, CI: 0.63, 0.97), 1L immunomodulator (HR: 0.39, CI: 0.22, 0.69), 1L proteasome inhibitor (HR: 1.4, CI: 1.1, 1.8), and 1L SCT (HR: 0.22, CI: 0.15, 0.32) as significant predictors of rapid disease progression. Conclusions: Our study provides important insights comparing high risk populations with MM treated in the real-world setting. A higher proportion of CHR patients received 1L SCT and this provided the longest 1L TTNT as compared to other treatments. In 2L, among patients not receiving 2L SCT, we observed a trend towards significantly longer TTNT provided by dara-based treatment as compared to non-dara based treatment; however, our TTNT is lower than progression-free survival results observed in pivotal trials. We identified potential underlying differences in our patient populations that may be driving the predictors of rapid disease progression, including 1L SCT eligibility and renal disease, and these will be further investigated in propensity score matched populations. Future research will continue to explore optimal treatment sequences in high-risk populations with multiple myeloma to improve patient outcomes. These data highlight an urgent need to better predict FHR patients at diagnosis and develop clinical trials incorporating novel compounds in high risk patients. Figure 1 Figure 1. Disclosures Hansen: COTA, Inc.: Current Employment. Belli: COTA, Inc.: Current Employment, Other: Equity ownership. Goran: COTA, Inc.: Current Employment. Wang: COTA, Inc.: Current Employment, Other: Equity ownership.

scholarly journals Bortezomib for the treatment of multiple myeloma patients

2009 ◽  
Vol 13 (Suppl 1) ◽  
pp. 29-33 ◽  
Author(s):  
C Green ◽  
J Bryant ◽  
A Takeda ◽  
K Cooper ◽  
A Clegg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Disease Progression ◽  
Survival Curve ◽  
Controlled Trial ◽  
High Dose ◽  
Single Technology Appraisal ◽  
High Dose Dexamethasone ◽  
The Cost

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bortezomib for the treatment of multiple myeloma patients at first relapse and beyond, in accordance with the licensed indication, based upon the evidence submission from Ortho Biotech to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturer’s definition of the decision problem were time to disease progression, response rate, survival and quality of life. The literature searches for clinical and cost-effectiveness studies were adequate and the one randomised controlled trial (RCT) included was of reasonable quality. Results from the RCT suggest that bortezomib increases survival and time to disease progression compared with high-dose dexamethasone (HDD) in multiple myeloma patients who have had a relapse after one to three treatments. Cost-effectiveness analysis based on the same trial and an observational study was reasonable and gave an estimated cost per life-year gained of £30,750, which ranged from £27,957 to £36,747 on sensitivity analysis. An attempt was made to replicate the results of the manufacturer’s model and to compare the results to the Kaplan–Meier survival curve presented in the manufacturer’s submission. In addition, a one-way sensitivity analysis and a probabilistic sensitivity analysis were undertaken, as well as additional scenario analyses. Based on these analyses the ERG suggests that the cost-effectiveness results presented in the manufacturer’s submission may underestimate the cost per life-year gained for bortezomib therapy (versus high-dose dexamethasone) when potential UK practice and scenarios are considered. The guidance issued by NICE in June 2006 as a result of the STA states that bortezomib monotherapy for the treatment of relapsed multiple myeloma is clinically effective compared with HDD but has not been shown to be cost-effective and is not recommended for the treatment of progressive multiple myeloma in patients who have received at least one previous therapy and who have undergone, or are unsuitable for, bone marrow transplantation.

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