A Prospective Study of Circulating Chemokines and Angiogenesis Markers and Risk of Multiple Myeloma and Its Precursor

Abstract Background Experimental and clinical studies have implicated certain chemokines and angiogenic cytokines in multiple myeloma (MM) pathogenesis. To investigate whether systemic concentrations of these markers are associated with future MM risk and progression from its precursor, monoclonal gammopathy of undetermined significance (MGUS), we conducted a prospective study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods We measured concentrations of 45 immunologic and pro-angiogenic markers in sera from 241 MM case patients, 441 participants with nonprogressing MGUS, and 258 MGUS-free control participants using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. We also evaluated absolute risk of progression using weighted Kaplan-Meier estimates. All statistical tests were two-sided. Results Prediagnostic levels of six markers were statistically significantly elevated among MM case patients compared with MGUS-free control participants using a false discovery rate of 10% (EGF, HGF, Ang-2, CXCL12, CCL8, and BMP-9). Of these, three angiogenesis markers were associated with future progression from MGUS to MM: EGF (fourth vs first quartile: OR = 3.01, 95% CI = 1.61 to 5.63, Ptrend = .00028), HGF (OR = 2.59, 95% CI = 1.33 to 5.03, Ptrend = .015), and Ang-2 (OR = 2.14, 95% CI = 1.15 to 3.98, Ptrend = .07). A composite angiogenesis biomarker score substantially stratified risk of MGUS progression to MM beyond established risk factors for progression, particularly during the first 5 years of follow-up (areas under the curve of 0.71 and 0.64 with and without the angiogenesis marker score, respectively). Conclusions Our prospective findings provide new insights into mechanisms involved in MM development and suggest that systemic angiogenesis markers could potentially improve risk stratification models for MGUS patients.

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Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Blood ◽

10.1182/blood-2008-12-194241 ◽

2009 ◽

Vol 113 (22) ◽

pp. 5412-5417 ◽

Cited By ~ 579

Author(s):

Ola Landgren ◽

Robert A. Kyle ◽

Ruth M. Pfeiffer ◽

Jerry A. Katzmann ◽

Neil E. Caporaso ◽

...

Keyword(s):

Multiple Myeloma ◽

Monoclonal Gammopathy ◽

Population Based ◽

Serum Samples ◽

M Proteins ◽

Cancer Screening Trial ◽

Risk Of Progression ◽

Study Population ◽

A Prospective Study ◽

Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.

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P-146: A prospective study of conventional skeletal survey versus Whole-body CT for osteolytic lesions in Multiple Myeloma

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/s2152-2650(21)02273-4 ◽

2021 ◽

Vol 21 ◽

pp. S115

Author(s):

Michael Gundesen ◽

Jon Thor Asmussen ◽

Einar Haukås ◽

Michael Schubert ◽

Niels Abildgaard ◽

...

Keyword(s):

Multiple Myeloma ◽

Prospective Study ◽

Skeletal Survey ◽

Whole Body ◽

Osteolytic Lesions ◽

Whole Body Ct ◽

A Prospective Study ◽

Body Ct

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A prospective study of lenalidomide monotherapy for relapse after Allo-SCT for multiple myeloma

Bone Marrow Transplantation ◽

10.1038/bmt.2013.219 ◽

2014 ◽

Vol 49 (4) ◽

pp. 492-495 ◽

Cited By ~ 12

Author(s):

W I Bensinger ◽

D J Green ◽

N Burwick ◽

P S Becker

Keyword(s):

Multiple Myeloma ◽

Prospective Study ◽

A Prospective Study

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A prospective study of absolute risk and determinants of human papillomavirus incidence among young women in Costa Rica

BMC Infectious Diseases ◽

10.1186/1471-2334-13-308 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 6

Author(s):

Megan Clarke ◽

◽

Mark Schiffman ◽

Sholom Wacholder ◽

Ana Cecilia Rodriguez ◽

...

Keyword(s):

Human Papillomavirus ◽

Costa Rica ◽

Prospective Study ◽

Young Women ◽

Absolute Risk ◽

A Prospective Study

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A Prospective Study of Bortezomib in Combination with Melphalan and Prednisone for Patients with Previously Untreated Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.5181.5181 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5181-5181 ◽

Cited By ~ 1

Author(s):

Cristina Gasparetto ◽

George P. Keogh ◽

Jon P. Gockerman ◽

Mitchell Horwitz ◽

Joseph O. Moore ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Prospective Study ◽

Partial Remission ◽

Response Rate ◽

High Dose ◽

The Usa ◽

M Spike ◽

A Prospective Study ◽

Stem Cell Collection

Abstract The standard induction chemotherapy for patients with multiple myeloma (MM) is a dexamethasone based regimen including dexamethasone alone, VAD, thalidomide+dexamethasone and other combinations. Currently the overall response rate achieved with these regimens is ≤70% and the complete remission (CR) rate is <10%. In order to improve the CR rate for both transplant and non-transplant candidates, other agents and regimens are being explored. Bortezomib (Velcade), a proteasome inhibitor currently approved in the USA and in Europe for the treatment of relapsed/refractory MM, has demonstrated an impressive activity in the treatment of myeloma. In relapsed/refractory MM, bortezomib has achieved response rate of 35%, with a median duration of response and overall survival of 14 and 18 months, respectively. Clinical experience in relapsed/refractory MM and in previously untreated patients has suggested that the combination of bortezomib with other anti-myeloma drugs could further improve the results achieved with bortezomib alone. We have recently initiated a prospective study to assess the combination of velcade, melphalan and prednisone (MPV) in patients with previously untreated MM. The primary objectives of this study are toxicity, feasibility and CR rate after 4 cycles. The regimen consisted of bortezomib 1.3 mg/m2 iv on day 1,4,8,11. melphalan 6 mg/m2 po, and prednisone 60 mg/m2 po given on days 1 through 7 of each cycle. As July 2005, 11 patients have been recruited. The median age is 64 (48–74) and all patients were Durie-Salmon stage IIIA. Nine of the 11 patients have completed ≥2 cycles of therapy, 6 patients have completed all 4 cycles of therapy and 3 patients were withdrawn from study (2 for pneumonia and 1 for grade 3 orthostatic hypotension). The most common adverse events were neuropathy (grade 1–3), neutropenia (grade 1–3), thrombocytopenia (grade1–3), fatigue, and bowel changes. For the 6 patients that have completed all 4 cycles of MPV, the responses were: 2/6 CR (negative SPEP/IFE); 1/6 very good partial remission (VGPR, 90% reduction of M-spike) and 3/6 partial remission (PR, 50% reduction of the serum M-spike). For the 3 patients who have completed only 2 cycles of therapy so far, 1/3 achieved a VGPR and 2/3 achieved a PR. Three patients have proceeded to stem cell collection and all engrafted following high dose therapy. Although experience is still limited and follow-up short, other than 3 patients withdrawn from study, all patients treated with MPV have responded to treatment and 2/6 patients achieved a CR. The best response was observed after cycle 2 in the majority of patients. Stem cell collection and engraftment was successful in all attempts so far. These data indicate that bortezomib combined with a short term alkylating regimen should be further explored as an induction regimen before transplantation in patients with myeloma.

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