Leading Article | Published:

International uniform response criteria for multiple myeloma

  • A Corrigendum to this article was published on 22 November 2006
  • A Corrigendum to this article was published on 25 April 2007

Abstract

New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma.

Introduction

There is an increasing need for widely accepted, reproducible criteria to evaluate response in multiple myeloma.1, 2 Several different systems are currently in use, but are not exactly comparable. For example, the US cooperative groups ECOG and SWOG have differing systems, as do several European groups, such as the MRC (UK)3 and the IFM (France).4 In addition, the European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry/American Bone Marrow Transplant Registry (EBMT/IBMTR/ABMTR) developed widely used criteria, commonly referred to as the EBMT criteria.5 However, as discussed below, there is a need to update prior criteria.

The need for new uniform response criteria has been triggered by several factors (Table 1). The most pressing need is for criteria that facilitate precise comparisons between new treatment strategies. Better criteria are also required for use in the clinic at the individual patient level. In this setting, clarification of complete response (CR) is particularly important. As more active agents are available, there is a need to assess not just if response has occurred, but the exact magnitude of response. There is increased awareness of the distinction between surrogate end points such as reduction in M-component level and more clinical end points such as recovery of functional status or organ function, length of response and overall survival duration.6

Table 1 Rationale for the development of uniform response criteria

Many of the commonly used criteria do not define CR stringently. In the EBMT criteria, CR does not require absence of monoclonal (M) plasma cells, but rather the reduction in plasma cells to 5% or less on bone marrow samples. This naturally results in the contamination of a subset of complete responders with normal polyclonal plasma cells in the marrow with those who still have M plasma cells. The latter are easily detected by kappa/lambda immunostaining or immunofluorescence studies using flow cytometry. Specific categories of CR with varying degrees of stringency allow greater precision in the definition of CR, enable comparison of the efficacy of various treatments including novel agents and csn permit the detection and monitoring of relapse more accurately. Existing criteria lack sufficient detail, which as a result allows substantial investigator discretion, and lead to inaccuracies in the estimated response rate. For example, the EBMT criteria require specific reductions in M-protein levels for each category of response, but the minimum level of M-protein that is required in the serum and urine to allow accurate response assessment is not specified. Similarly, it is not clear from prior criteria how patients with ‘unmeasurable’ levels of urine M-protein should be monitored for response evaluation.

Finally, present criteria allow limited assessment of response in patients with oligo-secretory or non-secretory myeloma.7 Response in these patients can now be assessed using the sensitive serum free light-chain (FLC) assay (Freelite, Binding Site). Incorporation of the serum FLC assay into the response criteria for myeloma allows inclusion and evaluation of these patients in clinical trials.

Development of new response and relapse criteria

The International Myeloma Working Group has developed new standard diagnostic criteria8 and a new International Staging System (ISS) for multiple myeloma,9 which are being widely accepted as the current standards for diagnosis and staging. The development of the new response criteria proposed in this manuscript started with a meeting of the International Myeloma Working Group (participants are listed at the end of the manuscript) during the 10th International Myeloma Workshop, Sydney, 10–14 April 2005. Based on the discussions and decisions made at this meeting, the criteria were formulated and drafted by two of the authors (BGD and SVR) and circulated to the members of the Working Group and revised. Final approval was made at a meeting of the International Myeloma Working Group at the Annual Meeting of the American Society of Hematology, Atlanta, GA, USA, December 2005 and subsequent reviews of this paper.

A summary of the important changes in the new criteria versus prior systems is provided in Table 2. It is important to point out that for patients with measurable M-protein levels in the serum and urine, the definitions of complete and partial response as well as disease progression match those used in the EBMT (Bladé) criteria. Therefore, although important clarifications are added, for all practical purposes, in trials that include only patients with measurable disease response rates and progression, estimates reported using the using the new International Myeloma Working Group criteria will be comparable to those using the EBMT criteria. This will allow easy comparison of rates reported in trials using the EBMT criteria with those using the new criteria. The most important changes in the new criteria are (1) addition of a new category of stringent CR that is of significant importance given rapid advances in therapy, (2) addition of response criteria for interpreting the serum FLC assay, which will enable numerous patients hitherto excluded from clinical trials for lack of measurable disease to enter and be evaluated on clinical trials, and (3) formal addition of a category of very good partial response (VGPR) to allow distinction of patients with excellent responses that may have outcomes similar to those patients considered to be in CR.

Table 2 Summary of similarities and specific changes introduced in the New Uniform Response Criteria compared to the EBMT/IBMTR Criteria

Diagnostic criteria for multiple myeloma

The need for clear baseline diagnostic criteria cannot be overemphasized. Three recent publications from the International Myeloma Working Group incorporate recommended methods for diagnosis, baseline staging and prognostic classifications as well as disease subtype identification.1, 8, 9 With these systems, the features of patients entering clinical trials can be clearly delineated. Table 3 summarizes the diagnostic criteria for active myeloma.

Table 3 Diagnostic criteria for multiple myeloma requiring systemic therapy

Response categories

Changes in the M-component level are the principal indicators used for response evaluation.6 It is important to note that M-component is a surrogate marker and its use is accompanied by all the pitfalls that can potentially detract from such use including variations in marker synthesis, metabolism or release as well as myeloma cell heterogeneity with respect to M-component production.10 The major response categories include CR, partial response (PR), stable disease (SD), progressive disease (PD) and relapse from CR (see Tables 5 and 6).

Table 5 International Myeloma Working Group uniform response criteria: CR and other response categories
Table 6 International Myeloma Working Group uniform response criteria: disease progression and relapse

Additional subcategories have been used by a number of investigators.3, 11 The subcategories of near complete response (nCR) and VGPR have been integrated into the new criteria under one single category termed ‘VGPR’. Importantly, the term ‘stable disease’ is not recommended for use as a measure of treatment efficacy; instead time to progression (TTP) and response duration estimates (see below) should be used in instances when the stability of disease with a particular therapy needs to be highlighted. TTP is calculated from the start of treatment and includes all patients entering the trial. Duration of response (DOR) is calculated from the time of first recorded achievement of a particular response level, that is, PR, VGPR, CR or sCR (see Table 5), and includes only responding patients. Although documentation of response requires a confirmatory measurement, the start time for DOR is the first date at which response was noted.

Important aspects of response assessment

Table 4 summarizes important practical details in response assessment. In addition, two specific points must be emphasized. Firstly, checking the M-component level at each cycle during induction is critically important in the evaluation of novel therapies to determine the speed of response, which may have clinical implications. For example, with several new regimens, response occurs rapidly and can be substantial within 1–2 months.12, 13 The second point is that the new criteria eliminate the need for consecutive confirmations 6 weeks apart currently required for response testing. A DOR of 6 weeks does not carry major clinical significance and is not a surrogate for durability of response. The main concern is to eliminate laboratory or other error; this can be carried out by the requirement of a confirmatory test at any time following the first test provided it is before any new/non-protocol therapy. The importance of response, that is, its durability, should be highlighted by reporting data on TTP and DOR. Thus plateau phase can be documented by indicating the TTP and/or DOR.1

Table 4 Practical details of response evaluation

Three other aspects pertaining to the serum FLC assay deserve emphasis. First, the serum FLC assay (Freelite, The Binding Site, Birmingham, UK) is a highly sensitive marker of light chains in circulation that are unbound to intact immunoglobulin, and the FLC ratio is an excellent indicator of clonality.14 Thus, normalizing of serum FLC ratio is a stricter indicator of CR, and may correlate well with extended response duration15 (Kumar S et al. Blood 2005; 106: 971a, abs 3479). Note that in patients with renal insufficiency, the levels of both the kappa and lambda may remain elevated, but the ratio normalizes with achievement of CR. Second, in order to minimize chance of error, FLC response is not assessable for patients who start with low baseline serum FLC assay levels below 10 mg/dl (<100 mg/l). Third, although the serum FLC assay is a very reliable test, it is important to closely monitor laboratory variation.16 Strict guidelines are required with regard to usage times for the serum FLC assay kits. It should also be noted that serum FLC assay testing might be useful in the prognostic and response evaluation of patients who also have a measurable serum and/or urine M-component in the future, given its recently reported prognostic value in M-gammopathy of undetermined significance (MGUS).17

The international Myeloma Working Group Uniform Response Criteria

The International Myeloma Working Group Uniform Response Criteria are listed in Table 5. Under CR two categories are listed: CR and stringent (sCR). The CR category is available for widespread use and provides continuity with prior systems. However, sCR, the more stringent category, allows more accurate assessment of new therapies. Many myeloma groups already use this latter category. It is now possible to specifically list and clearly identify which categories are used. The major goal is to foster studies evaluating correlations between stringent CR and durable response and prolonged survival.

VGPR, as defined in IFM trials,4 has been very slightly modified to also include what has been called nCR. Use of VGPR has several advantages including the reliance upon the 90% or higher regression cutoff, which is simpler to implement than use of immunofixation positivity versus negativity, an observer-dependent assessment. In addition, failure to achieve VGPR correlates with inferior outcome.1 The definition of PR except for inclusion of the FLC assay for the subgroup of patients with ‘unmeasurable’ disease is similar to the EBMT criteria. It is important to note that the FLC assay should not be used to assess response in patients with measurable levels of M-protein in either serum or urine. Such patients should be assessed using standard criteria; the serum light-chain assay is only applicable to those patients who do not have either 1 g/dl or higher M-protein in the serum or 200 mg/day or higher M-protein level in the urine. Less than PR is identified as SD, which can be clinically meaningful, but is not sufficient as an indicator of response benefit in new therapeutic trials. Reporting SD or response categories less than PR as meaningful is not recommended in clinical trials of new agents. Overall, the emphasis is upon simplicity, reproducibility and the awareness that very fine discriminations are frequently unreliable and not clinically meaningful.

The criteria for PD and relapse from CR are listed in Table 6. A category of clinical relapse has been added for optional assessment in clinical trials and for use in clinical practice. Progressive disease will continue to identify patients in whom the standard M-component (and related) criteria for relapse or disease progression have been met. Progressive disease is the end point that is used for calculating TTP and progression-free survival (PFS) in trials, and mirrors the EBMT criteria. One problem is that progression defined using these criteria may or may not reflect a need for therapy (or new therapy). Early re-treatment can be unnecessary, result in unwanted toxicities and underestimate the benefit of prior treatment, as true symptomatic relapse may not emerge until months or years later. Thus, discrete ‘event categories’ are required to identify relapse or progression requiring intervention. These ‘events’ are broadly the same as the CRAB categories used for diagnosis of myeloma. Various nuances and details related to use in the relapse setting are outlined in Table 6. Thus, where possible, reporting of time to re-treatment and/or time to clinical relapse would be useful; as mentioned earlier, these definitions will also be useful in clinical practice. It is anticipated that new trials will use clinical relapse as an end point and ‘time to clinical relapse’ as a hallmark of clinical utility of therapy.

The difficulties and nuances in evaluating myeloma-related events are well known. It is important to re-emphasize that myeloma must be the cause of events. Whatever additional testing is required to confirm myeloma relatedness is strongly encouraged. This may include magnetic resonance imaging, computed tomography and/or fluoro-18-deoxyglucose (FDG)/positron emission tomography (PET) imaging (Walker R et al. Blood 2004; 104: 217a, abs 758).18, 19

Survival end points

DOR is an important end point and can predict ultimate overall survival (Tricot G et al. Blood 2004; 104: 265a, abs 926).6, 20, 21, 22 Several different methods are used to calculate response duration and the impact of treatment.

  • PFS: PFS is the time from start of the treatment to disease progression or death. This encompasses all patients and has been considered a surrogate marker for overall survival duration. This is the recommended method to present trial results.

  • Event-free survival (EFS): The definition for EFS depends on how ‘event’ is defined. In some studies, this can be the same as PFS. EFS can also include additional ‘events’ that are considered to be of importance besides death, including serious drug toxicity. EFS is not recommended for general use unless specifically defined, as confusion can arise about the details of additional ‘events’. PFS is preferred.

  • TTP: This is the time from start of treatment to disease progression with deaths owing to causes other than progression not counted, but censored. This is a helpful method to discretely assess the durability of treatment benefit.

  • Disease-free survival (DFS): DFS applies to patients in CR, and is measured from the start of CR to the time of relapse from CR. This parameter has limited value in myeloma at present.

  • DOR: DOR applies to patients achieving at least PR by the criteria in Table 5, and is measured from start of achieving PR (first observation of PR before confirmation) to the time of disease progression, with deaths owing to causes other than progression not counted, but censored. This is an additional parameter for consideration in the assessment of new agents and/or new comprehensive treatment strategies. DOR and TTP are the recommended ways of establishing the durability of response. As noted above, investigators now have the option to consider ‘clinical relapse’ as a valuable end point.

Overall survival

Many recent myeloma trials have had response and/or TTP as the primary end points. However, overall survival and quality of life reflect the full impact of therapies. Several factors limit the use of overall survival as the ultimate end point.

  • Over 5 years of follow-up are required to assess benefit.

  • Initial response and TTP may or may not translate into overall survival benefit.

  • New agents used as part of induction, consolidation/transplant and/or maintenance are frequently used at time of relapse in the ‘control’ (non-use) arm of trials. Thus the comparison is with early versus later use. There has been no widely accepted plan or framework to control for this.

  • Additional new agents are now being introduced, which can further impact outcome assessment.

The problems involved are illustrated by several trials (Tricot G et al. Blood 2004; 104: 265a, abs 926)23, 24, 25 (Barlogie B et al. Blood 2004; 104: 156a, abs 538).26, 27, 28, 29 In the SWOG trial,26 high-dose cyclophosmide was utilized for stem cell harvesting in both arms of the trial and ultimately over half the patients in the non-transplant arm ended up being transplanted. Likewise, in a very recent trial reported by the Arkansas group,27 thalidomide was used as part of the TT-2 in one arm of the trial and produced a significantly higher CR rate and disease-free interval. However, overall survival was not improved. But, it is important to note that 83% of patients not in the thalidomide arm received thalidomide at relapse. Thus, again the study reflects an unplanned ‘early’ versus ‘later’ use of a therapeutic intervention, in this case thalidomide. In a more minor way, this was also an issue in the recently published28 results of the melphalan/prednisone (MP) versus MP thalidomide trial. In this case, there was survival benefit with addition of thalidomide. Only 21% of patients in the non-thaldiomide group had received thalidomide at the time of relapse. But, again, this was not a planned part of the trial. New trial designs to evaluate survival duration must accommodate these types of complexity. These details are further discussed in a recent review.1

Conclusions

The response criteria outlined in this paper are expected to be used widely in future clinical trials of myeloma. The major new additions to the response criteria are categories of stringent CR, VGPR and incorporation of the serum FLC assay to evaluate patients with oligo-secretory disease. The criteria also clarify several inconsistencies in prior response criteria, make confirmation of response and disease progression easier to perform with less chance of deviations, and define time to event end points that are critical in the evaluation of outcome.

Additional information

Please see Corrigendum. The PDF and HTML versions of this article remain uncorrected.

Please click on the abstract or full text for the link to the corrigendum attached to this article. Please note the article and PDF have not been corrected.

References

  1. 1

    Durie BGM . New approaches to treatment for multiple myeloma: durable remission and quality of life as primary goals . Clin Lymphoma Myeloma 2005 ; 6 : 181 – 190 .

  2. 2

    Rajkumar SV, Dispenzieri A . Evaluation and monitoring of response to therapy in multiple myeloma . Haematologica 2005 ; 90 : 1305 – 1308 .

  3. 3

    Child JA, Morgan G, Davies F, Owen RG, Bell SE, Hawkins K et al . High-dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma . N Engl J Med 2003 ; 348 : 1875 – 1883 .

  4. 4

    Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al . Single versus double autologous stem-cell transplantation for multiple myeloma . N Engl J Med 2003 ; 26 : 2495 – 2502 .

  5. 5

    Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al . Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation . Br J Haematol 1998 ; 102 : 1115 – 1123 .

  6. 6

    Durie BGM, Jacobson J, Barlogie B, Crowley J . Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in Southwest Oncology Group chemotherapy trials . J Clin Oncol 2004 ; 22 : 1857 – 1863 .

  7. 7

    Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Therneau TM, Larson DR et al . POEMS syndrome: definitions and long-term outcome . Blood 2003 ; 101 : 2496 – 2506 .

  8. 8

    International Myeloma Working Group . Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group . Br J Haematol 2003 ; 121 : 749 – 757 .

  9. 9

    Greipp PR, San Miguel J, Durie BGM, Crowley J, Barlogie B, Blade J et al . International staging system for multiple myeloma . J Clin Oncol 2005 ; 23 : 3412 – 3420 .

  10. 10

    Durie BGM . Staging and kinetics in multiple myeloma . In: Salmon SE (ed). Clinics in Haematology: Myeloma and Related Disorders, Vol. 2, Number 1, WB Saunders Company, Ltd: Alden Press, Ocford, 1982, pp 3 – 18 .

  11. 11

    Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al . A phase II study of bortezomib in relapsed, refractory myeloma . N Engl J Med 2003 ; 348 : 2609 – 2617 .

  12. 12

    Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M et al . PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma . Br J Haematol 2005 ; 129 : 755 – 762 .

  13. 13

    Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR . Serum free light chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma . Blood 2001 ; 97 : 2900 – 2902 .

  14. 14

    Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT . Serum testing for assessment of patients with Bence–Jones myeloma . Lancet 2003 ; 361 : 489 – 491 .

  15. 15

    Mead GP, Carr-Smith HD, Drayson MT, Morgan GJ, Child A, Bradwell AR . Serum free light chains for monitoring multiple myeloma . Br J Haematol 2004 ; 126 : 348 – 354 .

  16. 16

    Hassoun H, Reich L, Klimek VM, Dhodapkar M, Cohen A, Kewalramani T et al . Doxorubicin and dexmaethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma . Br J Hematol 2006 ; 132 : 155 .

  17. 17

    Rajkumar SV, Kyle RA, Therneau TM, Melton III LJ, Bradwell AR, Clark RJ et al . Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance . Blood 2005 ; 106 : 812 – 817 .

  18. 18

    Kyle RA, Schreiman JS, McLeod RA, Beabout JW . Computed tomography in diagnosis and management of multiple myeloma and its variants . Arch Int Med 1985 ; 145 : 1451 – 1452 .

  19. 19

    Durie BGM, Waxman AD, D'Angeloa A, William CM . Whole body F-FDG18 PET identifies high-risk myeloma . J Nucl Med 2002 ; 43 : 1457 – 1463 .

  20. 20

    Durie BGM . Is magnitude of initial response predictive for survival in multiple myeloma? Ann Oncol 1999 ; 2 : 166 – 169 .

  21. 21

    Lahuerta JJ, Martinez-Lopez J, de la Serna J, Blade J, Grande C, Alegra A et al . Remission status defined by immunofixation versus electrophoresis following autologus transplantation has a major impact on the outcome of multiple myeloma patients . Br J Haematol 2000 ; 109 : 438 – 446 .

  22. 22

    Riccardi A, Mora O, Tinelli C, Porta C, Danova M, Brugnatelli S et al . Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomized protocol . Eur J Cancer 2003 ; 39 : 31 – 37 .

  23. 23

    Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D et al . Superiority of thalidomide and dexamethasone over vincristine–doxorubicin–dexmaethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma . Blood 2005 ; 106 : 359 .

  24. 24

    Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer E, Facon T et al . Bortezomib or high-dose dexamethasone for relapsed multiple myeloma . N Engl J Med 2005 ; 352 : 2487 – 2498 .

  25. 25

    Rajkumar SV, Dispenzieri A . Evaluation and monitoring of response to therapy in multiple myeloma . Haematologica 2005 ; 90 : 1305 – 1308 .

  26. 26

    Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD et al . Standard chemotherapy compared with high dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup trial S9321 . J Clin Oncol 2006 ; 24 : 929 – 936 .

  27. 27

    Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al . Thalidomide and hematopoietic-cell transplantation for multiple myeloma . N Engl J Med 2006 ; 354 : 1021 – 1030 .

  28. 28

    Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V et al . Oral melphalan and prednisone therapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: a randomized controlled trial . Lancet 2006 ; 367 : 825 – 831 .

  29. 29

    Alexanian R, Weber D, Giralt S, Dimopoulos M, Delasalle K, Smith T et al . Impact of complete remission with intensive therapy in patients with responsive multiple myeloma . Bone Marrow Transplant 2001 ; 27 : 1037 – 1043 .

Download references

Author information

Correspondence to B G M Durie or S V Rajkumar.

Appendix A.

Appendix A.

International myeloma working group:

Raymond Alexanian, MD Anderson, Houston, Texas

Kenneth Anderson, DFCI, Boston, Massachusetts

Michael Attal, Purpan Hospital, Toulouse, France

Herve Avet-Loiseau, Institute de Biologie, Nantes, France

Leif Bergsagel, Mayo Clinic Scottsdale

Joan Bladé, Hospital Clinica, Barcelona, Spain

Bart Barlogie, MIRT UAMS Little Rock, Arkanas

Regis Batille, Nantes, France

Meral Beksac, Ankara University, Turkey

Andrew Belch, Cross Cancer Institute, Canada

Mario Boccadoro, University of Torino

Michele Cavo, Bologna, Italy

Tony Child, United Kingdom

Ray Comenzo, Memorial-Sloan Kettering Cancer Center, New York

John Crowley, Cancer Research and Biostatistics, Seattle, Washington

William Dalton, H Lee Moffitt, Tampa, Florida

Faith Davies, Royal Marsden Hospital, London, England

Meletios Dimopoulos, Alexandra Hospital, Athens, Greece

Angela Dispenzieri, Mayo Clinic, Rochester, Minnesota

Brian Durie, Cedars-Sinai Outpatient Medical Center, Los Angeles, California

Theirry Facon, Centre Hospitalier Regional Universitaire de Lille, France

Dorotea Fantl, Buenos Aires, Argentina

Jean-Paul Fermand, Paris, France

Rafael Fonseca, Mayo Clinic Scottsdale, Scottsdale, Arizona

Gosta Gahrton, Karolinska Institutet, Stockholm , Sweden

Morie Gertz, Mayo Clinic

Hartmut Goldschmidt, Heidelberg, Germany

Philip Greipp, Mayo Clinic

Roman Hajek, Brno University, Brno, Czech Republic

Jean-Luc Harousseau, Institute de Biologie, Nantes, France

Kim Hawkins, Statistician, United Kingdom

Martin Hjorth, Data manager, Netherlands

Vania Hungria, Clinica San Germano, Sao Paolo, Brazil

Mohamad Hussein, The Cleveland Clinic, Cleveland, Ohio, USA

Peter Jacobs, South Africa

Mariana Juni, Fundaleu, Buenos Aires, Argentina

Douglas Joshua, Royal Prince Alfred Hospital, Sydney, Australia

Michael Katz, New York

Michio Kawano, Yamaguchi University, Ube, Japan

Shaji Kumar, Mayo Clinic

Robert Kyle, Mayo Clinic

Juan Lahuerta, Madrid, Spain

Henk Lokhorst, University Hospital, Utrecht, The Netherlands

Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna

Jayesh Mehta, Northwestern University, Chicago

Giampaolo Merlini, University of Pavia, Pavia, Italy

Philippe Moreau, Nantes, France

Gareth Morgan, Royal Marsden Hospital, London

Antonio Palumbo, Cathedra Ematologia, Torino, Italy

Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina

Amara Nouel, Bolivar, Venezuela

Susie Novis, IMF, Los Angeles, California

Raymond Powles, Leukaemia & Myeloma, Wimbledon

Linda Pilarski, The University of Alberta, Edmonton Alberta, Canada

S Vincent Rajkumar, Mayo Clinic

Tony Reiman, Cross Cancer Institute, Canada

Paul Richardson, Dana Farber Cancer Institute, Boston, Massachusetts

Angelina Rodriquez Morales, Bonco MetroPolitano de Sangre, Caracas, Venezuela

Kazuyuki Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan

David Siegel, Hackensack, Cancer Center, Hackensack, New Jersey

Guido Tricot, MIRT UAMS, Little Rock, Arkansas

Jesus San Miguel, University of Salamanca

Seema Singhal, Northwestern University

Pieter Sonneveld, Erasmus University Hospital, Rotterdam, The Netherlands

Keith Stewart, Mayo Clinic Scottsdale

Patrizia Tosi, Bologna, Italy

Ingemar Turesson, Malmo, Sweden

Ivan Van Riet, Brussels Vrija University

David Vesole, St Vincent's Comprehensive Cancer Center, New York

Donna Weber, MD Anderson, Houston, Texas

Jan Westin, University of Gothenberg, Sweden

Keith Wheatley, University of Birmingham, Edgbaston, Birmingham, UK

Brian Van Ness, University of Minnesota

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • myeloma
  • response criteria
  • staging
  • survival duration
  • uniform criteria
  • clinical outcomes

Further reading