Evaluation of the R2‐ISS in real‐world patients with newly diagnosed multiple myeloma: A nationwide cohort study by the Korean Multiple Myeloma Working Party (KMM 2202)
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ABSTRACT:
SUBMITTER: Cho H
PROVIDER: S-EPMC10878185 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.
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| S-EPMC10344481 | biostudies-literature
Project description:Our prior studies identified the prognostic significance of quantifying cPCs by multiparametric flow cytometry (MFC) in newly diagnosed multiple myeloma (NDMM) patients. We evaluated if a similar quantification of cPCs could add prognostic value to the current R-ISS classification of 556 consecutive NDMM patients seen at the Mayo Clinic, Rochester from 2009 to 2017. Those patients that had ≥5 cPCs/μL and either R-ISS stage I or stage II disease were re-classified as R-ISS IIB stage for the purposes of this study. The median time to next therapy (TTNT) and overall survival (OS) for patients with ≥5 cPCs/μL at diagnosis was as follows: R-ISS I (N = 110) - 40 months and not reached; R-ISS II (N = 69) - 30 and 72 months; R-ISS IIB (N = 96) - 21 and 45 months and R-ISS III (N = 281) - 20 and 47 months respectively. Finally, ≥ 5 cPCs/μL retained its adverse prognostic significance in a multivariable model for TTNT and OS. Hence, quantifying cPCs by MFC can potentially enhance the R-ISS classification of a subset of NDMM patients with stage I and II disease by identifying those patients with a worse than expected survival outcome.
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Project description:Despite the development of novel therapeutic agents, multiple myeloma (MM) remains incurable, owing mainly to inevitable relapse in almost all patients. Some relapses occur as extramedullary disease (EMD), which is rare but is the most aggressive event in MM patients. Extramedullary myeloma (EMM) has extraordinary heterogeneous biological and clinical features. Previous studies have shown that expression levels of LncRNAs and mRNAs in different stages of MM are different. This study analyzes the expression levels of LncRNAs and mRNAs in primary plasma cells (PCs) from MM and EMM patients.
2023-03-01 | GSE147841 | GEO
Project description:The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P < 0.001, and 21.5 vs. 60.9 months, P < 0.001, respectively). Primary PCL diagnosed using the revised criteria presented with higher total calcium levels and serum creatinine levels, lower platelet counts and frequent organomegaly and plasmacytoma at diagnosis. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum β2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs ≥ 5% in a peripheral blood smear is appropriate for PCL diagnosis.
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Project description:The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.
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Project description:DNA Hydroxymethylation is Associated with Disease Severity and Persists at Enhancers of Oncogenic Regions in Multiple Myeloma
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Project description:Patients with transplant-ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28-day treatment cycle: pomalidomide (4 mg/day on days 1-21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64-86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7-9.0) and 18.48 months (95% CI, 9.4-27.6), respectively. The incidence rate of grade ≥ 3 non-hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment-associated infection is the main cause of morbidity and mortality.
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Project description:We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (≥2; P<0.001). In a comparison of patients with single sites with patients without the disease, up-front transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: P=0.86, and extramedullary organ: P=0.88). In single paraskeletal involvement, this translated less clearly into worse 3-year overall survival (P=0.07) while single organ involvement was significantly worse (P=0.001). Multiple organ sites were associated with worse outcome (P<0.001 and P=0.01). First-line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (P=0.13 for both).
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