Current Issues in Cancer: Multiple myeloma

MacLennan, Ian C. M.; Drayson, Mark T.; Dunn, Janet A.

doi:10.1136/bmj.308.6935.1033

Cited by 30 publications

(3 citation statements)

References 32 publications

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“…MM is differentiated from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) by the presence of end-organ damage (4, 5). The clinical symptoms of MM range from asymptomatic forms to manifestations of anemia, bone pain, and eventually spontaneous of fractures, renal failure, and frequent infections (6–8). Thanks to the introduction of novel agents (proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies), the management strategies for MM have been improved considerably in the past decade (9–12).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a 9-Gene Prognostic Signature in Patients With Multiple Myeloma

Yin

Meng

et al. 2019

Front. Oncol.

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Background: Multiple myeloma (MM) is one of the most common types of hematological malignance, and the prognosis of MM patients remains poor.Objective: To identify and validate a genetic prognostic signature in patients with MM.Methods: Co-expression network was constructed to identify hub genes related with International Staging System (ISS) stage of MM. Functional analysis of hub genes was conducted. Univariate Cox proportional hazard regression analysis was conducted to identify genes correlated with the overall survival (OS) of MM patients. Least absolute shrinkage and selection operator (LASSO) penalized Cox proportional hazards regression model was used to minimize overfitting and construct a prognostic signature. The prognostic value of the signature was validated in the test set and an independent validation cohort.Results: A total of 758 hub genes correlated with ISS stage of MM patients were identified, and these hub genes were mainly enriched in several GO terms and KEGG pathways involved in cell proliferation and immune response. Nine hub genes (HLA-DPB1, TOP2A, FABP5, CYP1B1, IGHM, FANCI, LYZ, HMGN5, and BEND6) with non-zero coefficients in the LASSO Cox regression model were used to build a 9-gene prognostic signature. Relapsed MM and ISS stage III MM was associated with high risk score calculated based on the signature. Patients in the 9-gene signature low risk group was significantly associated with better clinical outcome than those in the 9-gene signature high risk group in the training set, test, and validation set.Conclusions: We developed a 9-gene prognostic signature that might be an independent prognostic factor in patients with MM.

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Section: Introductionmentioning

confidence: 99%

Development and Validation of a 9-Gene Prognostic Signature in Patients With Multiple Myeloma

Yin

Meng

et al. 2019

Front. Oncol.

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“…Multiple myeloma is a clonal neoplasm of bone marrow plasma cells. Over 2000 people in the U.K. die with this disease annually with an average survival from diagnosis of between 2 and 3 years ( MacLennan et al , 1994 ). Following initial chemotherapy multiple myeloma can exist in a clinically stable state known as plateau phase.…”

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MRC trial of α2b‐interferon maintenance therapy in first plateau phase of multiple myeloma

Drayson¹,

Chapman²,

Dunn

et al. 1998

Br J Haematol

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Plateau phase has been achieved in 64% of all newly diagnosed patients with multiple myeloma treated with the ABCM (adriamycin, BiCNU, cyclophosphamide and melphalan) regimen in the Medical Research Council (MRC) trials; this stable clinical stage of the disease is associated with no more than minimal symptoms. Several studies have found that α‐interferon (α‐IFN) maintenance therapy increases the duration of plateau phase, but it is less clear if this translates into prolonged survival. We report the effect of α‐IFN on the duration of plateau phase and overall survival in a trial with 284 patients who were randomized to receive α2b‐IFN (Intron‐A) or no maintenance therapy during first plateau phase. The minimum follow‐up after randomization was 21 months. There was no significant difference in the overall survival between the two treatment groups (χ2 = 0.32, P = 0.57). There was a trend towards longer relapse‐free survival in the patients allocated α‐IFN, but this trend to longer plateau phase was not statistically significant (χ2 = 1.62, P = 0.2). Disease progression at relapse on α‐IFN appears to be more severe with greater elevations from plateau levels of serum paraprotein (P = 0.06) and β2‐microglobulin (P = 0.03) levels. Physicians tended to start chemotherapy sooner after diagnosis of relapse when patients had received α‐IFN (P = 0.16). Although, in common with most other studies, there is a trend for patients treated with α‐IFN to have a longer plateau phase, this is counteracted by morbidity attributable to the treatment and a somewhat shortened survival post relapse. Meta‐analysis of interferon trials is required to assess whether the minor trend for longer survival in patients maintained on α‐IFN found in some studies is significant and, if so, the extent of this advantage.

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“…EDITOR, - In their detailed review on developments in the treatment of multiple myeloma, Ian C M MacLennan and colleagues briefly discussed the results of allogeneic bone marrow transplantation, in particular mentioning the reported high mortality related to the procedure 1. Our own experience of allogeneic bone marrow transplantation for myeloma is different.…”

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confidence: 99%