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multiple myeloma mayo

David Dingli, Sikander Ailawadhi, P Leif Bergsagel, Francis K Buadi, Angela Dispenzieri, Rafael Fonseca, Morie A Gertz, Wilson I Gonsalves, Susan R Hayman, Prashant Kapoor, Taxiarchis Kourelis, Shaji K Kumar, Robert A Kyle, Martha Q Lacy, Nelson Leung, Yi Lin, John A Lust, Joseph R Mikhael, Craig B Reeder, Vivek Roy, Stephen J Russell, Taimur Sher, A Keith Stewart, Rahma Warsame, Stephen R Zeldenrust, S Vincent Rajkumar, Asher A Chanan Khan
Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy...
April 2017: Mayo Clinic Proceedings
N Tandon, S V Rajkumar, B LaPlant, A Pettinger, M Q Lacy, A Dispenzieri, F K Buadi, M A Gertz, S R Hayman, N Leung, R S Go, D Dingli, P Kapoor, Y Lin, Y L Hwa, A L Fonder, M A Hobbs, S R Zeldenrust, J A Lust, W I Gonsalves, S J Russell, S K Kumar
We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration. The median estimated follow up was 5 and 2...
February 17, 2017: Blood Cancer Journal
Siyang Leng, Suzanne Lentzsch
In a 2008 paper, Dispenzieri and colleagues at the Mayo Clinic proposed a risk stratification system for patients with smoldering multiple myeloma (SMM) based on the presence of three risk factors: serum M-protein ≥3 g/dL, bone marrow plasma cell percentage ≥10%, and a free light chain (FLC) ratio (κ to λ) of either ≤0.125 or ≥8. The patient in this vignette has all three risk factors, classifying him as high-risk, with an associated median time to progression (TTP) of 1.9 years. This is significantly worse than a patient with intermediate-risk (median TTP 5...
December 2016: Seminars in Oncology
Yi L Hwa, Qian Shi, Shaji K Kumar, Martha Q Lacy, Morie A Gertz, Prashant Kapoor, Francis K Buadi, Nelson Leung, David Dingli, Ronald S Go, Suzanne R Hayman, Wilson I Gonsalves, Stephen Russell, John A Lust, Yi Lin, S Vincent Rajkumar, Angela Dispenzieri
A preclinical study demonstrated anti-proliferative and apoptotic effect of propranolol on multiple myeloma (MM) cell. Clinical studies suggested that beta-blocker (BB) might impact the prognosis of breast, prostate, colorectal, ovarian, lung, and skin cancer. This retrospective study evaluated the effect of BB in MM disease-specific survival (DSS) and overall survival (OS). Among 1,971 newly diagnosed MM patients seen at Mayo Clinic between 1995 and 2010, usage of BB and other cardiac (or antihypertensive) medications were abstracted...
January 2017: American Journal of Hematology
Jonas Paludo, Utkarsh Painuly, Shaji Kumar, Wilson I Gonsalves, Vincent Rajkumar, Francis Buadi, Martha Q Lacy, Angela Dispenzieri, Robert A Kyle, Michelle L Mauermann, Arleigh McCurdy, David Dingli, Ronald S Go, Suzanne R Hayman, Nelson Leung, John A Lust, Yi Lin, Morie A Gertz, Prashant Kapoor
INTRODUCTION: Limited data exist with respect to the outcome and optimal treatment of patients with myelomatous involvement of the central nervous system (CNS). MATERIALS AND METHODS: Of 4060 patients with multiple myeloma (MM), evaluated at Mayo Clinic from 1998 to 2014, 29 (0.7%) had identifiable CNS involvement, established by the presence of atypical plasma cells in the cerebrospinal fluid (CSF) and/or identification of intraparenchymal or meningeal involvement on magnetic resonance imaging (MRI)...
November 2016: Clinical Lymphoma, Myeloma & Leukemia
Paolo Milani, S Vincent Rajkumar, Giampaolo Merlini, Shaji Kumar, Morie A Gertz, Giovanni Palladini, Martha Q Lacy, Francis K Buadi, Suzanne R Hayman, Nelson Leung, David Dingli, John A Lust, Yi Lin, Prashant Kapoor, Ronald S Go, Yi L Hwa, Wilson I Gonsalves, Steven R Zeldenrust, Robert A Kyle, Angela Dispenzieri
Multiple myeloma (MM) patient frailty has been delineated primarily by age and ECOG performance score (PS) and recently by the IMWG frailty score based on functional status [Activity of Daily Living (ADL) and Instrumental-ADL scores], comorbidities [Charlson-comorbidity-index (CCI)] and age. It was hypothesized that N-terminal natriuretic peptide type B (NT-proBNP) might be both a more convenient measure of frailty and a predictor of overall survival (OS). Three-hundred and fifty-one consecutive symptomatic MM patients who were seen at Mayo Clinic within 30 days of diagnosis and who had blood stored were eligible...
November 2016: American Journal of Hematology
W I Gonsalves, S V Rajkumar, A Dispenzieri, D Dingli, M M Timm, W G Morice, M Q Lacy, F K Buadi, R S Go, N Leung, P Kapoor, S R Hayman, J A Lust, S J Russell, S R Zeldenrust, L Hwa, T V Kourelis, R A Kyle, M A Gertz, S K Kumar
The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to MM. The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013...
January 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Martha Grogan, Morie Gertz, Arleigh McCurdy, Lindsey Roeker, Robert Kyle, Sudhir Kushwaha, Richard Daly, Joseph Dearani, Richard Rodeheffer, Robert Frantz, Martha Lacy, Suzanne Hayman, Christopher McGregor, Brooks Edwards, Angela Dispenzieri
AIM: To determine the outcome of orthotopic heart transplantation (OHT) in immunoglobulin light chain (AL) amyloidosis. METHODS: The medical records of patients with AL who underwent orthotopic heart transplantation at the Mayo Clinic in Rochester Minnesota from 1992 to 2011 were reviewed. Patients met at least one of the following at: New York Heart Association class IV heart failure, ventricular thickness > 15 mm, ejection fraction < 40%. Selection guidelines for heart transplant included age < 60 years, absence of multiple myeloma and significant extra-cardiac organ involvement...
June 24, 2016: World Journal of Transplantation
Damien Guinault, Emmanuel Canet, Antoine Huart, Arnaud Jaccard, David Ribes, Laurence Lavayssiere, Marion Venot, Olivier Cointault, Murielle Roussel, Marie-Béatrice Nogier, Claire Pichereau, Virginie Lemiale, Bertrand Arnulf, Michel Attal, Dominique Chauveau, Elie Azoulay, Stanislas Faguer
Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs...
September 2016: British Journal of Haematology
Wilson I Gonsalves, Michael M Timm, S Vincent Rajkumar, William G Morice, Angela Dispenzieri, Francis K Buadi, Martha Q Lacy, David Dingli, Nelson Leung, Prashant Kapoor, Robert A Kyle, Morie A Gertz, Shaji K Kumar
Evaluation of clonal plasma cells (PCs) in the bone marrow (BM) of multiple myeloma (MM) patients reveals two distinct clonal PC populations based on the presence or absence of CD45 expression. We explored the prognostic significance of CD45 expression by clonal PCs in the BM of MM patients in the era of novel agent therapy. All 156 MM patients seen at the Mayo Clinic, Rochester from 2009 to 2011 who had their BM evaluated by multiparametric flow cytometry were included. Patients whose BM had ≥20% of the clonal PCs expressing CD45 were classified as CD45 positive (+) and the rest as CD45 negative (-)...
May 2016: Leukemia Research
Angela Dispenzieri, Francis Buadi, Shaji K Kumar, Craig B Reeder, Tamur Sher, Martha Q Lacy, Robert A Kyle, Joseph R Mikhael, Vivek Roy, Nelson Leung, Martha Grogan, Prashant Kapoor, John A Lust, David Dingli, Ronald S Go, Yi Lisa Hwa, Suzanne R Hayman, Rafael Fonseca, Sikander Ailawadhi, P Leif Bergsagel, Ascher Chanan-Khan, S Vincent Rajkumar, Stephen J Russell, Keith Stewart, Steven R Zeldenrust, Morie A Gertz
Immunoglobulin light chain amyloidosis (AL amyloidosis) has an incidence of approximately 1 case per 100,000 person-years in Western countries. The rarity of the condition not only poses a challenge for making a prompt diagnosis but also makes evidenced decision making about treatment even more challenging. Physicians caring for patients with AL amyloidosis have been borrowing and customizing the therapies used for patients with multiple myeloma with varying degrees of success. One of the biggest failings in the science of the treatment of AL amyloidosis is the paucity of prospective trials, especially phase 3 trials...
August 2015: Mayo Clinic Proceedings
Elad Ziv, Eric Dean, Donglei Hu, Alessandro Martino, Daniel Serie, Karen Curtin, Daniele Campa, Blake Aftab, Paige Bracci, Gabriele Buda, Yi Zhao, Jennifer Caswell-Jin, Robert Diasio, Charles Dumontet, Marek Dudziński, Laura Fejerman, Alexandra Greenberg, Scott Huntsman, Krzysztof Jamroziak, Artur Jurczyszyn, Shaji Kumar, Djordje Atanackovic, Martha Glenn, Lisa A Cannon-Albright, Brandt Jones, Adam Lee, Herlander Marques, Thomas Martin, Joaquin Martinez-Lopez, Vincent Rajkumar, Juan Sainz, Annette Juul Vangsted, Marzena Wątek, Jeffrey Wolf, Susan Slager, Nicola J Camp, Federico Canzian, Celine Vachon
Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 × 10(-10)). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0...
July 22, 2015: Nature Communications
Moritz Binder, S Vincent Rajkumar, Morie A Gertz, Martha Q Lacy, Angela Dispenzieri, Francis K Buadi, David Dingli, Suzanne R Hayman, John A Lust, Prashant Kapoor, Yi Lin, Ronald S Go, Yi L Hwa, Robert A Kyle, Shaji K Kumar
Response to therapy in newly diagnosed symptomatic multiple myeloma (NDMM) can impact long-term outcomes. It is not clear if baseline laboratory parameters can predict an early, deep response. Totally 1,304 patients with NDMM seen between 2001 and 2013 at Mayo Clinic Rochester were studied. The association between baseline laboratory parameters and early, deep response defined as a very good partial response or better (VGPR+) within four cycles of treatment was investigated. Multivariable logistic regression was used to assess the associations between the parameters of interest and response...
October 2015: American Journal of Hematology
Muhammad A Mir, Prashant Kapoor, Shaji Kumar, Shivlal Pandey, Angela Dispenzieri, Martha Q Lacy, David Dingli, William Hogan, Francis Buadi, Suzanne Hayman, Manish Gandhi, Morie A Gertz
BACKGROUND: Allogeneic transplant in myeloma remains controversial. PATIENTS AND METHODS: We performed a retrospective review of 76 patients in the Mayo Clinic database from 1993 to 2013 who underwent allogeneic hematopoietic stem cell transplant (HSCT) for myeloma. RESULTS: After excluding ineligible patients, among the remaining 66 patients, median age at transplant was 42 years and 87% had residual disease at the time of transplant. Myeloablative (71%) versus reduced intensity conditioning (29%), matched sibling donors (70%) versus unrelated donors showed no outcome difference...
June 2015: Clinical Lymphoma, Myeloma & Leukemia
W I Gonsalves, N Leung, S V Rajkumar, A Dispenzieri, M Q Lacy, S R Hayman, F K Buadi, D Dingli, P Kapoor, R S Go, Y Lin, S J Russell, J A Lust, S Zeldenrust, R A Kyle, M A Gertz, S K Kumar
Renal impairment (RI) is seen in over a quarter of patients with newly diagnosed multiple myeloma (NDMM). It is not clear if reversal of RI improves the outcome to that expected for NDMM patients without RI. We evaluated 1135 consecutive patients with NDMM seen at the Mayo Clinic between January 2003 and December 2012. RI was defined as having a creatinine clearance (CrCl) <40ml/min. The median overall survival (OS) for patients with RI at diagnosis receiving and not receiving novel agent induction therapy was not reached vs 46 months (P<0...
2015: Blood Cancer Journal
Joseph R Mikhael, Craig B Reeder, Edward N Libby, Luciano J Costa, P Leif Bergsagel, Francis Buadi, Angela Mayo, Sravan K Nagi Reddy, Katherine Gano, Amylou C Dueck, A Keith Stewart
Sixty-four transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300 mg/m(2) cyclophosphamide (days 1, 8, 15), 100 mg thalidomide (days 1-28) and 40 mg dexamethasone (days 1, 8, 15, 22) in 28-day cycles (CYKLONE regimen). Carfilzomib was dose-escalated to 15/20, 20/27, 20/36 and 20/45 mg/m(2) to determine the maximum tolerated dose (MTD), which was 20/36 mg/m(2) . Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%)...
April 2015: British Journal of Haematology
A J Greenberg, S Philip, A Paner, S Velinova, A Badros, R Catchatourian, R Ketterling, R A Kyle, S Kumar, C M Vachon, S V Rajkumar
We examined four clinically assessed cytogenetic subtypes (t(11;14), t(4;14), monosomy 13/del13q and monosomy 17/del17p in 292 black patients with newly diagnosed multiple myeloma (MM) from four medical centers, who had fluorescent in situ hybridization testing results available in their medical records. We then compared the prevalence of these abnormalities with a previously characterized Mayo Clinic cohort of 471 patients with MM. We found a significant difference in the prevalence of the t(11;14) immunoglobulin heavy chain (IgH) translocation between blacks and whites, 6...
January 2, 2015: Blood Cancer Journal
Robert A Kyle, Dirk R Larson, Terry M Therneau, Angela Dispenzieri, L Joseph Melton, Joanne T Benson, Shaji Kumar, S Vincent Rajkumar
BACKGROUND: Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain protein. About 15-20% of patients with multiple myeloma secrete monoclonal light chains only, without expression of the normal immunoglobulin heavy chain, which constitutes light-chain multiple myeloma. The definition, prevalence, and progression of these premalignant phases of light-chain multiple myeloma have not been fully characterised. We aimed to identify a subset of patients with idiopathic Bence Jones proteinuria who had a high risk of progression to light-chain multiple myeloma analogous to that seen in patients with smouldering multiple myeloma...
October 1, 2014: Lancet Haematology
Shaji K Kumar, Betsy LaPlant, Wee Joo Chng, Jeffrey Zonder, Natalie Callander, Rafael Fonseca, Briant Fruth, Vivek Roy, Charles Erlichman, A Keith Stewart
Dysregulation of cyclin-dependent kinases is a hallmark of myeloma, and specifically, cdk5 inhibition can enhance the activity of proteasome inhibitors in vitro. Dinaciclib is a novel potent small molecule inhibitor of cyclin-dependent kinases (CDK)1, CDK2, CDK5, and CDK9. Patients with relapsed multiple myeloma and ≤5 prior lines of therapy, with measurable disease, were enrolled. Dinaciclib was administered on day 1 of a 21-day cycle at doses of 30 to 50 mg/m(2). Overall, 27 evaluable patients were accrued; the median number of prior therapies was 4...
January 15, 2015: Blood
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September 2014: Mayo Clinic Health Letter
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