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1. Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance

Author

Clay-Gilmour, A, Hildebrandt, MAT, Brown, EE, Hofmann, JN, Spinelli, JJ, Giles, GG, Cozen, W, Bhatti, P, Wu, X, Waller, RG, Belachew, AA, Robinson, DP, Norman, AD, Sinnwell, JP, Berndt, S, Rajkumar, SV, Kumar, SK, Chanock, SJ, Machiela, MJ, Milne, RL, Slager, SL, Camp, NJ, Ziv, E, Vachon, CM, Clay-Gilmour, A, Hildebrandt, MAT, Brown, EE, Hofmann, JN, Spinelli, JJ, Giles, GG, Cozen, W, Bhatti, P, Wu, X, Waller, RG, Belachew, AA, Robinson, DP, Norman, AD, Sinnwell, JP, Berndt, S, Rajkumar, SV, Kumar, SK, Chanock, SJ, Machiela, MJ, Milne, RL, Slager, SL, Camp, NJ, Ziv, E, and Vachon, CM

Abstract

So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE] ±0.04) and 15% (SE ±0.11) for MM and MGUS risk, respectively, and a 55% (SE ±0.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR], 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.

Published
2020

9. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

Author

Dispenzieri, A, Kyle, R, Merlini, G, Miguel, JS, Ludwig, H, Hajek, R, Palumbo, A, Jagannath, S, Blade, J, Lonial, S, Dimopoulos, M, Comenzo, R, Einsele, H, Barlogie, B, Anderson, K, Gertz, M, Harousseau, JL, Attal, M, Tosi, P, Sonneveld, P, Boccadoro, M, Morgan, G, Richardson, P, Sezer, O, Mateos, MV, Cavo, M, Joshua, D, Turesson, I, Chen, W, Shimizu, K, Powles, R, Rajkumar, SV, and Durie, BGM

Published
2009

15. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: A study of the International Myeloma Working Group

Author

Hillengass, J Moulopoulos, LA Delorme, S Koutoulidis, V Mosebach, J Hielscher, T Drake, M Rajkumar, SV Oestergaard, B Abildgaard, N others

Subjects
Health Sciences, otorhinolaryngologic diseases, Επιστήμες Υγείας
Abstract

For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P

Published
2017

16. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma

Author

Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, Harousseau J, Zonder JA, Zangari M, Attal M, Belch A, Knop S, JoshuaD, Sezer O, Ludwig H, Vesole D, Bladé J, Kyle R, Westin J, Weber D, Bringhen S, Niesvizky R, Waage A, von Lilienfeld Toal M, Lonial S, Morgan GJ, Orlowski RZ, Shimizu K, Anderson KC, Boccadoro M, Durie BG, Sonneveld P, Hussein MA, International Myeloma Working Group, CAVO, MICHELE, Radiology & Nuclear Medicine, Hematology, Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, Harousseau J, Zonder JA, Cavo M, Zangari M, Attal M, Belch A, Knop S, JoshuaD, Sezer O, Ludwig H, Vesole D, Bladé J, Kyle R, Westin J, Weber D, Bringhen S,Niesvizky R, Waage A, von Lilienfeld-Toal M, Lonial S, Morgan GJ, Orlowski RZ,Shimizu K, Anderson KC, Boccadoro M, Durie BG, Sonneveld P, Hussein MA, and International Myeloma Working Group.

Subjects
Cancer Research, medicine.medical_specialty, Premedication, Population, Antineoplastic Agents, Risk Assessment, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, medicine, Humans, International Normalized Ratio, cardiovascular diseases, Risk factor, education, Lenalidomide, Dexamethasone, Multiple myeloma, education.field_of_study, Aspirin, business.industry, Warfarin, Thrombosis, Venous Thromboembolism, Hematology, Heparin, Low-Molecular-Weight, medicine.disease, Thalidomide, Surgery, Oncology, Multiple Myeloma, business, medicine.drug
Abstract

The incidence of venous thromboembolism (VTE) is more than 1 per thousand annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients withor = 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis.

Published
2008

17. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma

Author

Stewart, Ak, Rajkumar, Sv, Dimopoulos, Ma, Masszi, T, Špička, I, Oriol, A, Hájek, R, Rosiñol, L, Siegel, Ds, Mihaylov, Gg, Goranova Marinova, V, Rajnics, P, Suvorov, A, Niesvizky, R, Jakubowiak, Aj, San Miguel JF, Ludwig, H, Wang, M, Maisnar, V, Minarik, J, Bensinger, Wi, Mateos, Mv, Ben Yehuda, D, Kukreti, V, Zojwalla, N, Tonda, Me, Yang, X, Xing, B, Moreau, P, Palumbo, A, Petrini, Mario, Aspire, Investigators, Laboratory of Molecullar and Cellular Therapy, and Clinical sciences

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Kaplan-Meier Estimate, Dexamethasone, Ixazomib, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Intention to Treat Analysis, Middle Aged, Multiple Myeloma, Oligopeptides, Recurrence, Thalidomide, Medicine (all), chemistry.chemical_compound, Internal medicine, 80 and over, medicine, Elotuzumab, Multiple myeloma, Lenalidomide, business.industry, General Medicine, Pomalidomide, medicine.disease, Carfilzomib, Surgery, chemistry, business, medicine.drug
Abstract

BACKGROUND: Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. METHODS: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. RESULTS: Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P

Published
2015

20. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib:A multicenter international myeloma working group study

Author

Kumar S. K., Lee J. H., Lahuerta J. J., Morgan G., Richardson P. G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S. K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J. S., Orlowski R., Palumbo A., Sezer O., Rajkumar S. V., Durie B. G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Chanan Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., CAVO, MICHELE, Kumar S.K., Lee J.H., Lahuerta J.J., Morgan G., Richardson P.G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S.K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J.S., Orlowski R., Palumbo A., Sezer O., Rajkumar S.V., Durie B.G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet-Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben-Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Cavo M, Chanan-Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García-Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., and Hematology

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, NATURAL HISTORY, Antineoplastic Agents, Context (language use), RELAPSE, Article, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Elotuzumab, Survival analysis, Multiple myeloma, Aged, Aged, 80 and over, Isatuximab, Bortezomib, business.industry, Hematology, Middle Aged, Pomalidomide, medicine.disease, Survival Analysis, Surgery, Regimen, SURVIVAL, Disease Progression, Female, Multiple Myeloma, business, medicine.drug
Abstract

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011

Published
2012

22. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

Author

Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, CAVO, MICHELE, Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, Cavo M, Hematology, and Radiology & Nuclear Medicine

Subjects
Cancer Research, medicine.medical_specialty, Myeloma protein, health care facilities, manpower, and services, education, Asymptomatic, Monoclonal Gammopathy of Undetermined Significance, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, AL amyloidosis, Humans, Risk factor, Multiple myeloma, health care economics and organizations, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Macroglobulinemia, Hematology, medicine.disease, Prognosis, 3. Good health, Surgery, Oncology, 030220 oncology & carcinogenesis, Serum protein electrophoresis, Practice Guidelines as Topic, Disease Progression, medicine.symptom, business, Multiple Myeloma, Monoclonal gammopathy of undetermined significance
Abstract

International Myeloma Working Group22.-- et al., Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein

Published
2010

23. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)

Author

Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL, Kumar S, Munshi NC, Dispenzieri A, Kyle R, Merlini G, San Miguel J, Ludwig H, Hajek R, Jagannath S, Blade J, Lonial S, Dimopoulos MA, Einsele H, Barlogie B, Anderson KC, Gertz M, Attal M, Sonneveld P, Boccadoro M, Morgan G, Sezer O, Mateos MV, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Richardson PG, Niesvizky R, Rajkumar SV, Durie BG, IMWG, TOSI, PATRIZIA, CAVO, MICHELE, Radiology & Nuclear Medicine, Hematology, Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL, Kumar S, Munshi NC, Dispenzieri A, Kyle R, Merlini G, San Miguel J, Ludwig H, Hajek R, Jagannath S, Blade J, Lonial S, Dimopoulos MA, Einsele H, Barlogie B, Anderson KC, Gertz M, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Richardson PG, Niesvizky R, Rajkumar SV, Durie BG, and IMWG.

Subjects
Oncology, Benzylamines, Cancer Research, medicine.medical_specialty, Anti-HIV Agents, medicine.medical_treatment, Context (language use), Hematopoietic stem cell transplantation, Cyclams, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Heterocyclic Compounds, Internal medicine, medicine, Humans, Autologous transplantation, Multiple myeloma, business.industry, Plerixafor, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Hematopoietic Stem Cell Mobilization, 3. Good health, Transplantation, 030220 oncology & carcinogenesis, Immunology, Blood Component Removal, Stem cell, Multiple Myeloma, business, 030215 immunology, medicine.drug
Abstract

Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as well as the role of autologous stem cell transplantation in this disease. On June 1, 2008, a panel of experts was convened by the International Myeloma Foundation to address issues regarding stem cell mobilization and autologous transplantation in myeloma in the context of new therapies. The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions.

Published
2009

24. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens

Author

Kumar, S, Giralt, S, Stadtmauer, Ea, Harousseau, Jl, Palumbo, Antonio, Bensinger, W, Comenzo, Rl, Lentzsch, S, Munshi, N, Niesvizky, R, San Miguel, J, Ludwig, H, Bergsagel, L, Blade, J, Lonial, S, Anderson, Kc, Tosi, P, Sonneveld, P, Sezer, O, Vesole, D, Cavo, M, Einsele, H, Richardson, Pg, Durie, Bg, Rajkumar, Sv, International Myeloma Working Group, Radiology & Nuclear Medicine, Hematology, Kumar S, Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL, Lentzsch S, Munshi N, Niesvizky R, San Miguel J, Ludwig H, Bergsagel L, Blade J, Lonial S, Anderson KC, Tosi P, Sonneveld P, Sezer O, Vesole D, Cavo M, Einsele H, Richardson PG, Durie BG, Rajkumar SV, and International Myeloma Working Group.

Subjects
Oncology, medicine.medical_specialty, Consensus Development Conferences as Topic, medicine.medical_treatment, Immunology, Antineoplastic Agents, Hematopoietic stem cell transplantation, Medical Oncology, Biochemistry, Bortezomib, Autologous stem-cell transplantation, Internal medicine, medicine, Humans, Lenalidomide, Multiple myeloma, Hematopoietic Stem Cell Mobilization, Clinical Trials as Topic, business.industry, Hematopoietic Stem Cell Transplantation, Cell Biology, Hematology, medicine.disease, Boronic Acids, Combined Modality Therapy, Thalidomide, Pyrazines, Stem cell, Multiple Myeloma, business, Immunosuppressive Agents, medicine.drug
Abstract

The past decade has witnessed a paradigm shift in the initial treatment of multiple myeloma with the introduction of novel agents such as thalidomide, lenalidomide, and bortezomib, leading to improved outcomes. High-dose therapy and autologous stem cell transplantation remains an important therapeutic option for patients with multiple myeloma eligible for the procedure. Before the advent of the novel agents, patients underwent stem cell collection prior to significant alkylating agent exposure, given its potential deleterious effect on stem cell collection. With increasing use of the novel agents in the upfront setting, several reports have emerged raising concerns about their impact on the ability to collect stem cells. An expert panel of the International Myeloma Working Group (IMWG) was convened to examine the implications of these therapies on stem collection in patients with myeloma and to develop recommendations for addressing these issues. Here we summarize the currently available data and present our perspective on the problem and potential options to overcome this problem. Specifically, we recommend early mobilization of stem cells, preferably within the first 4 cycles of initial therapy, in patients treated with novel agents and encourage participation in clinical trials evaluating novel approaches to stem cell mobilization. (Blood. 2009;114:1729-1735)

Published
2009

25. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

Author

Kumar, Sk, Lee, Jh, Lahuerta, Jj, Morgan, G, Richardson, Pg, Crowley, J, Haessler, J, Feather, J, Hoering, A, Moreau, P, Leleu, X, Hulin, C, Klein, Sk, Sonneveld, P, Siegel, D, Bladé, J, Goldschmidt, H, Jagannath, S, Miguel, Js, Orlowski, R, Palumbo, Antonio, Sezer, O, Rajkumar, Sv, Durie, Bg, on behalf of the International Myeloma Working Group, International Myeloma Working Group, Abildgaard, N, Abonour, R, Alexanian, R, Alsina, M, Anderson, Kc, Attal, M, Avet Loiseau, H, Badros, A, Baris, D, Barlogie, B, Bataille, R, Beksaç, M, Belch, A, Ben Yehuda, D, Bensinger, B, Leif Bergsagel, P, Bird, J, Boccadoro, M, Cavo, M, Chanan Khan, A, Ming Chen, W, Child, T, Chim, J, Chng, Wj, Comenzo, R, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimopoulos, M, Dispenzieri, A, Drach, J, Drake, M, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, García Sanz, R, Gasparetto, C, Gertz, M, Gibson, J, Giralt, S, Greipp, P, Hajek, R, Hardan, I, Hari, P, Harousseau, Jl, Hata, H, Hattori, Y, Heffner, T, Ho, J, Hungria, V, Ida, S, Jacobs, P, Johnsen, H, Jian, H, Joshua, D, Jurczyszyn, A, Kawano, M, Kröger, N, Kumar, S, Kyle, Ra, Lacy, M, Landgren, O, Laubach, J, Lentzsch, S, Lokhorst, H, Lonial, S, Ludwig, H, Maiolino, A, Mateos, M, Mehta, J, Mellqvist, Uh, Merlini, G, Mikhael, J, Morales, Ar, Nari, H, Munshi, N, Niesvizky, R, Nouel, A, Novis, Y, Palumbo, A, Pavlovsky, S, Pilarski, L, Powles, R, Raje, N, Vincent Rajkumar, S, Reece, D, Reiman, T, Roodman, D, Rosiñol, L, Shah, Jj, Shaughnessy, J, Shimizu, K, Shustik, C, Singhal, S, Spencer, A, Stadtmauer, E, Stewart, K, Terpos, E, Tosi, P, Tricot, G, Turesson, I, Van Camp, B, Van Ness, B, Van Riet, I, Broek, Iv, Vanderkerken, K, Vescio, R, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, and Zonder, J.

Published
2012

27. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1

Author

Rajkumar, SV, Harousseau, JL, Durie, B, Anderson, KC, Dimopoulos, M, Kyle, R, Blade, J, Richardson, P, Orlowski, R, Siegel, D, Jagannath, S, Facon, T, Avet-Loiseau, H, Lonial, S, Palumbo, AA, Zonder, J, Ludwig, H, Vesole, D, Sezer, O, Munshi, NC, San Miguel, J, and Radiology & Nuclear Medicine

Subjects
immune system diseases, hemic and lymphatic diseases
Abstract

It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma, detailed definitions for patient populations, lines of therapy, and specific endpoints. We propose that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript. (Blood. 2011; 117(18): 4691-4695)

Published
2011

30. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation

Author

Cavo, M, Rajkumar, Sv, Palumbo, Antonio, Moreau, P, Orlowski, R, Bladé, J, Sezer, O, Ludwig, H, Dimopoulos, Ma, Attal, M, Sonneveld, P, Boccadoro, Mario, Anderson, Kc, Richardson, Pg, Bensinger, W, Johnsen, He, Kroeger, N, Gahrton, G, Bergsagel, Pl, Vesole, Dh, Einsele, H, Jagannath, S, Niesvizky, R, Durie, Bg, San Miguel, J, Lonial, S, and International Myeloma Working Group

Published
2011

32. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study

Author

Kumar, Sk, Lee, Jh, Lahuerta, Jj, Morgan, G, Richardson, Pg, Crowley, J, Haessler, J, Feather, J, Hoering, A, Moreau, P, Leleu, X, Hulin, C, Klein, Sk, Sonneveld, P, Siegel, D, Bladé, J, Goldschmidt, H, Jagannath, S, Miguel, Js, Orlowski, R, Palumbo, Antonio, Sezer, O, Rajkumar, Sv, Durie, Bg, on behalf of the International Myeloma Working Group, International Myeloma Working Group, Abildgaard, N, Abonour, R, Alexanian, R, Alsina, M, Anderson, Kc, Attal, M, Avet Loiseau, H, Badros, A, Baris, D, Barlogie, B, Bataille, R, Beksaç, M, Belch, A, Ben Yehuda, D, Bensinger, B, Leif Bergsagel, P, Bird, J, Boccadoro, M, Cavo, M, Chanan Khan, A, Ming Chen, W, Child, T, Chim, J, Chng, Wj, Comenzo, R, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimopoulos, M, Dispenzieri, A, Drach, J, Drake, M, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, García Sanz, R, Gasparetto, C, Gertz, M, Gibson, J, Giralt, S, Greipp, P, Hajek, R, Hardan, I, Hari, P, Harousseau, Jl, Hata, H, Hattori, Y, Heffner, T, Ho, J, Hungria, V, Ida, S, Jacobs, P, Johnsen, H, Jian, H, Joshua, D, Jurczyszyn, A, Kawano, M, Kröger, N, Kumar, S, Kyle, Ra, Lacy, M, Landgren, O, Laubach, J, Lentzsch, S, Lokhorst, H, Lonial, S, Ludwig, H, Maiolino, A, Mateos, M, Mehta, J, Mellqvist, Uh, Merlini, G, Mikhael, J, Morales, Ar, Nari, H, Munshi, N, Niesvizky, R, Nouel, A, Novis, Y, Palumbo, A, Pavlovsky, S, Pilarski, L, Powles, R, Raje, N, Vincent Rajkumar, S, Reece, D, Reiman, T, Roodman, D, Rosiñol, L, Shah, Jj, Shaughnessy, J, Shimizu, K, Shustik, C, Singhal, S, Spencer, A, Stadtmauer, E, Stewart, K, Terpos, E, Tosi, P, Tricot, G, Turesson, I, Van Camp, B, Van Ness, B, Van Riet, I, Broek, Iv, Vanderkerken, K, Vescio, R, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, and Zonder, J.

Published
2011

35. International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

Author

Kyle, Ra, Durie, Bg, Rajkumar, Sv, Landgren, O, Blade, J, Merlini, G, Kröger, N, Einsele, H, Vesole, Dh, Dimopoulos, M, San Miguel, J, Avet Loiseau, H, Hajek, R, Chen, Wm, Anderson, Kc, Ludwig, H, Sonneveld, P, Pavlovsky, S, Palumbo, Antonio, Richardson, Pg, Barlogie, B, Greipp, P, Vescio, R, Turesson, I, Westin, J, and Boccadoro, Mario

Published
2010

37. Prevention of thalidomide and lenalidomide associated trombosis in myeloma

Author

Palumbo, Antonio, Rajkumar, Sv, Dimopoulos, Ma, Richardson, Pg, San Miguel, J, Barlogie, B, Harousseau, J, Zonder, Ja, Cavo, M, Zangari, M, Attal, M, Belch, A, Knop, S, Joshua, D, Sezer, O, Ludwig, H, Vesole, D, Bladé, J, Kyle, R, Westin, J, Weber, D, Bringhen, S, Niesvizky, R, Waage, A, Von Lilienfeld Toal, M, Lonial, S, Morgan, Gj, Orlowski, Rz, Shimizu, K, Anderson, Kc, Boccadoro, Mario, Durie, Bg, Sonneveld, P, and Hussein, Ma

Published
2008

38. SPOTLIGHT REVIEW

Author

Dimopoulos, MA Kastritis, E Rajkumar, SV

Subjects
Health Sciences, Επιστήμες Υγείας
Published
2008

39. Treatment of plasma cell dyscrasias with lenalidomide

Author

Dimopoulos, MA Kastritis, E Rajkumar, SV

Subjects
Health Sciences, Επιστήμες Υγείας
Abstract

Lenalidomide is an immunomodulatory drug, structurally related to thalidomide, with pleiotropic activity including antiangiogenic and antineoplastic properties. It is the product of advances in our understanding of the biology of myeloma cells, their interactions with the microenvironment and of the underlying molecular pathways. In preclinical and clinical studies, lenalidomide was more potent and less toxic than thalidomide. Subsequent phase II and III studies confirmed the activity of lenalidomide either as a single agent or in combination with dexamethasone in relapsed or refractory myeloma patients, whereas combinations with chemotherapy induce high response rates and durable remissions. Lenalidomide has been used successfully as an upfront treatment either with high or low dose dexamethasone or with melphalan and prednisone, resulting in high overall response and complete response rates and excellent 1-year survival. Lenalidomide causes less neuropathy than thalidomide; however, the risk of thromboembolism is high, especially in patients treated with lenalidomide and steroids. In this review, we summarize the mechanisms of action, toxicity and clinical activity, and the current role of lenalidomide in patients with multiple myeloma or other related plasma cell disorders.

Published
2008

41. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement

Author

Hussein, Ma, Vrionis, Fd, Allison, R, Berenson, J, Berven, S, Erdem, E, Giralt, S, Jagannath, S, Kyle, Ra, Legrand, S, Pflugmacher, R, Raje, N, Rajkumar, Sv, Randall, Rl, Roodman, D, Siegel, D, Vescio, R, Zonder, J, Durie, Bg, Alexanian R, International Myeloma Working G. r. o. u. p., Anderson, K, Attal, M, Avet Loiseau, H, Badros, A, Bergsagel, L, Bladé, J, Barlogie, B, Batille, R, Beksac, M, Belch, A, Bensinger, B, Boccadoro, M, Cavo, M, Chen, Wm, Child, T, Chim, J, Comenzo, R, Crowley, J, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimipoulous, M, Dispenzieri, A, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, Gertz, M, Gibson, J, Goldschmidt, H, Greipp, P, Hajek, R, Hardan, I, Harousseau, Jl, Hata, H, Hattori, Y, Ho, J, Hungria, V, Hussein, M, Ida, S, Jacobs, P, Jian, H, Joshua, D, Kawano, M, Kumar, S, Kyle, R, Lahuerta, J, Lee, Jh, Lokhorst, H, Ludwig, H, Leleu, X, Maiolino, A, Mehta, J, Merlini, G, Moreau, P, Morgan, G, Munshi, N, Palumbo, Antonio, Pavlovsky, S, Niesvizky, R, Novis, Y, Nouel, A, Powles, R, Pilarski, L, Reece, D, Reiman, T, Richardson, P, Morales, Ar, Sezer, O, Shaughnessy, J, Shimizu, K, Tricot, G, San Miguel, J, Singhal, S, Sonneveld, P, Shustik, C, Spencer, A, Stewart, K, Tosi, P, Turesson, I, Van Ness, B, Van Riet, I, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, Yehuda, Db, and Zonder, J.

Published
2008

43. Screening mammography in women aged 40-49 years

Author

Hartmann Lc and Rajkumar Sv

Subjects
Adult, Risk, medicine.medical_specialty, Screening mammography, business.industry, Breast cancer mortality, Absolute risk reduction, Age Factors, General Medicine, Middle Aged, medicine.disease, Breast cancer, Primary caregiver, Risk Factors, General partnership, Family medicine, Medicine, Humans, Mass Screening, False Positive Reactions, Female, business, Mammography, Randomized Controlled Trials as Topic
Abstract

Screening mammography in women aged 40-49 years reduces breast cancer mortality by 16%-18%, and is recommended by various national organizations. However, one must be aware of the recognized limitations of the approach. The actual benefit appears to be small (absolute risk reduction, 0.07%; the number of women who need to be screened to prevent 1 woman from dying of breast cancer, about 1,500-2,500), and there are associated risks and costs with this approach. The medical and scientific communities, in partnership with advocacy groups, must continue to work to improve our breast diagnostic capabilities, especially in younger women. Since this is an emotional and controversial issue, each woman will need to consider, with the aid of her primary caregiver, whether the risks of screening outweigh its potential benefits, and make an informed decision regarding screening.

Published
1999

44. A366 Relevance of Conventional Prognostic Factors in Multiple Myeloma (MM) in the Era of Novel Therapies

Author

Kapoor, P, primary, Kyle, RA, additional, Kumar, SK, additional, Rajkumar, SV, additional, Greipp, PR, additional, Witzig, TE, additional, Dispenzieri, A, additional, Lacy, MQ, additional, Lust, JA, additional, Hayman, SR, additional, Buadi, FK, additional, Zeldenrust, SR, additional, Dingli, D, additional, Russell, SJ, additional, and Gertz, MA, additional

Published
2009
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46. A247 Bortezomib, Dexamethasone, Cyclophosphamide, Lenalidomide (VDCR) Has High Efficacy in First-Line MM

Author

Kumar, S, primary, Flinn, Ian, additional, Noga, S, additional, Hari, R, additional, Rifkin, R, additional, Callander, N, additional, Bhandari, M, additional, Wolf, J, additional, Gasparetto, C, additional, Krishnan, A, additional, Grosman, D, additional, Glass, J, additional, Sahovic, EA, additional, Shi, J, additional, Webb, I, additional, Richardson, PG, additional, and Rajkumar, SV, additional

Published
2009
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47. A481 Long-Term Results of Single-Agent Thalidomide as Initial Therapy for Smoldering or Indolent Myeloma

Author

Short, KE Detweiler, primary, Hayman, SR, additional, Gertz, MA, additional, Lacy, MQ, additional, Dispenzieri, A, additional, Fonseca, R, additional, Kumar, S, additional, Zeldenrust, SR, additional, Russell, SJ, additional, Lust, JA, additional, Buadi, F, additional, Dingli, D, additional, Kyle, RA, additional, Greipp, PR, additional, Witzig, TE, additional, and Rajkumar, SV, additional

Published
2009
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49. A360 Skeletal Microstructural Changes in MGUS

Author

Drake, MT, primary, Ng, AC, additional, Charatcharoenwitthaya, N, additional, Kumar, SK, additional, Achenbach, SJ, additional, Holets, MF, additional, McCready, LK, additional, Rajkumar, SV, additional, and Kyle, RA, additional

Published
2009
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50. Laboratory persistence and clinical progression of small monoclonal abnormalities.

Author

Murray DL, Seningen JL, Dispenzieri A, Snyder MR, Kyle RA, Rajkumar SV, Katzmann JA, Murray, David L, Seningen, Justin L, Dispenzieri, Angela, Snyder, Melissa R, Kyle, Robert A, Rajkumar, S Vincent, and Katzmann, Jerry A

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) that presents with no quantifiable M spike on immunofixation electrophoresis (IFE) can be termed IFE MGUS. We retrospectively identified patients with IFE MGUS who were monitored with at least 1 subsequent assessment that included an IFE, and evaluated the persistence of the monoclonal protein and the progression of disease. Although the monoclonal proteins persisted in the majority of patients, 16% did not experience this persistence, and had no documented immunomodulatory therapy. After a median follow-up of 3.9 years, the disease clinically progressed in 14 patients (3.2%). Eight of these 14 patients with clinical progression had an immunoglobulin (Ig) A IFE M protein and 6 had an IgG M protein. This study demonstrates that in some patients with IFE MGUS, the M proteins are transient and that IgA IFE MGUS is more likely to persist and progress to myeloma. [ABSTRACT FROM AUTHOR]

Published
2012

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