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Originally published as JCO Early Release 10.1200/JCO.2004.05.111 on April 26 2004

Journal of Clinical Oncology, Vol 22, No 10 (May 15), 2004: pp. 1857-1863
© 2004 American Society of Clinical Oncology.
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Magnitude of Response With Myeloma Frontline Therapy Does Not Predict Outcome: Importance of Time to Progression in Southwest Oncology Group Chemotherapy Trials

Brian G.M. Durie, Joth Jacobson, Bart Barlogie, John Crowley

From the Cedars-Sinai Medical Center, Los Angeles, CA; Southwest Oncology Group Statistical Center, Cancer Research and Biostatistics, Seattle, WA; and Myeloma Institute for Research and Therapy, University of Arkansas for Medical Studies, Little Rock, AR.

Address reprint requests to Brian G.M. Durie, MD, Cedars-Sinai, 8201 Beverly Blvd, Los Angeles, CA 90048; e-mail: bdurie{at}salick.com


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors' Disclosures of...
 REFERENCES
 
PURPOSE: Four Southwest Oncology Group (SWOG) standard-dose chemotherapy protocols for multiple myeloma (MM) initiated between 1982 and 1992 were evaluated. The purpose was to clarify the predictive value of specific levels of myeloma-associated monoclonal protein reduction and time to first progression using mature data sets.

PATIENTS AND METHODS: Study data on 1,555 eligible previously untreated patients with MM enrolled onto SWOG phase III trials 8229, 8624, 9028, and 9210 were used in these analyses. Six-month and 12-month landmark analyses were performed to evaluate the outcome for patients in each response category.

RESULTS: The overall and event-free survivals for the four protocols combined were 33 months and 18 months, respectively. Using 6- and 12-month landmarks, the median survivals of 30 to 35 months were not different for responders (>= 50% and >= 75% regression) versus nonresponders in patients without disease progression before the landmarks. Conversely, at the 6- and 12-month landmarks, the median survivals for patients who had experienced disease progression were 13 and 15 months, respectively, versus a 34-month median for patients who did not experience progression. Using the Cox survival model, with response and progression considered as time-dependent covariates, survival duration was influenced more by the occurrence of progression than by the occurrence of response.

CONCLUSION: The magnitude of response, as a single variable, does not predict survival duration. Patients with response and stable disease have equivalent outcome. Only patients with progressive disease have a poorer outcome. The best indicator of survival is time to first progression.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors' Disclosures of...
 REFERENCES
 
Improvement in survival duration is the primary and most important evidence of benefit from therapy.1 Because treatment benefit is typically associated with reduction in myeloma-associated monoclonal protein (M-protein), quantitation of changes in M-protein levels has often been used as a surrogate marker of treatment outcome.2

During the 1980s, questions were raised about the validity of response criteria based on the percentage reduction in M-protein.3-7 Several studies showed that although achieving some degree of M-protein stabilization or reduction was important, the exact amount or percentage reduction was not directly correlated with the survival duration.3-7 In 1991, an editorial summarized the caution required in the interpretation of 50%, 75%, and 90% or higher levels of M-protein reduction with respect to treatment benefit.8 Complete remission, even true complete remission with negative bone marrow and markers, was not necessarily better than 50% reduction as far as survival duration improvement. In an effort to further clarify the predictive value of M-protein reduction as a surrogate marker of survival benefit, it was elected to perform landmark analyses using several Southwest Oncology Group (SWOG) studies.3 Using 6-month and 1-year landmarks, the impact of different levels of regression was evaluated. First progression of disease from the start of treatment was also evaluated as a surrogate marker of treatment benefit. Using these techniques, first progression, but not magnitude of M-protein reduction, was correlated with overall survival duration.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 Authors' Disclosures of...
 REFERENCES
 
Patient Population
Prestudy and serial follow-up data from four recent SWOG multiple myeloma phase III trials9-13 were used in these analyses (Table 1). Patients eligible for these studies had untreated, newly diagnosed multiple myeloma of any stage. SWOG study S822910 evaluated vincristine, melphalan, cyclophosphamide, and prednisone (VMCP)/vincristine, carmustine, doxorubicin, and prednisone (VBAP) for remission induction therapy followed by VMCP versus sequential half-body radiotherapy plus vincristine with prednisone in patients who achieved remission status with chemotherapy or sequential half-body radiotherapy plus vincristine with prednisone in patients who failed to achieve remission. SWOG study S862411 was a comparison of VMCP/VBAP with vincristine, doxorubicin, and dexamethasone (VAD) or vincristine, melphalan, cyclophosphamide, prednisone, and cisplain/vincristine, carmustine, doxorubicin, prednisone, and cisplatin for induction, followed by interferon alfa-2b or interferon alfa-2b plus prednisone for remission maintenance. The VAD plus verapamil plus quinine arm of study S902812 was closed early because of excessive mortality related to quinine toxicity. This arm was not included in these analyses. SWOG study S921013 compared VAD-prednisone with VAD-prednisone/quinine for induction, followed by a randomization of prednisone dose-intensity for remission maintenance.


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  		Table 1. Numbers of Registered and Eligible Patients in the Four SWOG Studies

 
End Points
The primary outcome of interest in these analyses is overall survival (OS). This is the measured time from initial study registration to time of death from any cause or last contact.

The response criteria were defined as follows: remission (previously identified as complete remission in SWOG criteria), >= 75% reduction in the calculated tumor mass, and if Bence-Jones protein is present, either a >= 90% reduction in this protein or reduction in the urine M-protein to less than 0.2 gm/d; partial remission (PR), 50% to 74% reduction, and if Bence-Jones protein is present, a 50% to 89% reduction. The calculated tumor mass is simply the measured specific quantitative immunoglobulin, except for immunoglobulin G disease, in which case a nomogram is used.1 Progression (progressive disease [PD]) was evaluated as follows: in nonresponding patients, progression is defined as a 25% increase over baseline in the calculated tumor mass or other signs of disease progression, such as hypercalcemia. In responding patients, progression was defined as the first occurrence of any of the following: an increase in calculated tumor mass by greater than 100% over the lowest level recorded; an increase to greater than the levels defining response; increase of lytic bone lesions or evidence of new disease activity. Stable disease (SD) was defined as less than 50% regression plus less than 25% progression and no evidence of new disease (progression) as noted above.

Statistical Methods
OS was calculated as the time from study registration to death from any cause or last contact. Event-free survival (EFS) was calculated as the time from study registration to either PD or death from any cause or last contact. Survival curves were estimated by the product-limit method14 and compared using the log-rank test.15 Cox proportional hazards regression with time-dependent covariates16 was used to assess the influence of response and progression on survival outcome, as was the landmark method.17 Landmark analyses specify a point in time (such as 6 months) to classify (by some parameter such as response) the patients still alive at that time point. Landmark analyses compare the subsequent differences in survival or EFS with regard to that response classification. Time-dependent Cox models attempt to summarize the evidence over all possible landmarks.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 Authors' Disclosures of...
 REFERENCES
 
Patient Characteristics
A total of 1,555 protocol-eligible patients were available for these analyses (Table 1). The median age was 62 years (range, 26 to 87 years); 61% of patients were men and 19% were African-American. Laboratory characteristics are presented in Table 2. Disease characteristics, including Durie-Salmon (DS) stage, are listed in Table 3. Laboratory variable distributions did not differ between the four studies, with a few notable exceptions. Serum ß2 microglobulin was higher in the older studies (65% >= 4 mg/L in S8229 v 57% >= 4 mg/L in S9210), as was hemoglobin (64% >= 10g/dL in S8229 v 46% >= 10g/dL in S9210). Although a similar number of patients had more than three lytic lesions in the four studies, a greater percentage of patients had no bone lesions in the more recent studies (25% in S9210) than the older studies (16% in S8229). Disease characteristics (eg, isotype, light chain isotype) were similar across studies.


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  		Table 2. Patient and Laboratory Characteristics Evaluated Collectively (N = 1,555)

 

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  		Table 3. Disease Characteristics of Patients in Four Studies (N = 1,555)

 
Median OS in the combined data set was 33 months. OS varied slightly between the four studies (Fig 1). OS by DS stage in this patient population is presented in Figure 2. Median OS by DS stage ranged from 57 months in stage I patients to 21 months in stage IIIB patients. Distribution of DS stage differed slightly between studies, with a smaller percentage of patients identified as either stage I/II or stage IIIB in the more recent studies (32% stage I/II in S8229 v 28% stage I/II in S9210; 24% stage IIIB in S8229 v 18% stage IIIB in S9210).



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  		Fig 1. Overall survival (A; median, 33 months) and event-free survival (B; median, 18 months) by Southwest Oncology Group multiple myeloma protocol. Median survivals range from 31 to 38 months without statistical differences.

 


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  		Fig 2. Overall survival from 6-month (A) and 1-year (B) landmarks by response category for patients who have not experienced disease progression at 6 months and 1 year. No statistically significant differences are evident.

 
OS and EFS
Figure 1 shows the OS and EFS for the four frontline protocols evaluated. No significant differences were observed. The median OS was 33 months and EFS was 18 months. Approximately 20% of patients are still in remission at 4 years and remain alive at 6 years. Conversely, 20% of patients die within the first year, and 35% of patients are no longer in remission at the end of the first year.

OS From 6-Month and 12-Month Landmarks Classified by Any Type of Response in Patients With No PD Before Landmark
Figure 2 shows the 6- and 12-month landmark survival curves for patients classified by response at the landmark time. Patients with PD before the landmark time were excluded in these analyses. Patients who experienced disease progression were analyzed separately (Fig 3). The median survivals for patients who have not experienced disease progression are essentially identical. Note that the survivals for patients who achieved remission (>= 75% regression), PR (>= 50% regression), and SD are not statistically different (Table 4).



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  		Fig 3. Overall survival from 6-month (A) and 1-year (B) landmarks by response category for patients who have experienced disease progression at 6 months and 1 year. The differences at 6 months and 1 year are both statistically significant (P < .0001). Resp, response; prog, progression.

 

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  		Table 4. Frequencies of Response and Progression by SWOG Protocol*

 
OS From 6-Month and 12-Month Landmarks Classified by Progression and Prior Response
Figure 3 shows the 6- and 12-month landmark survival curves for patients who have experienced disease progression, classified by primary disease progression (ie, no initial response) and patients with different levels of response before progression. The differences are significant overall (P < .0001). The worst median survivals of 4 or 5 months, respectively, were for patients having >= 50% or >= 75% decrease in M-protein followed by progression within the first 6 months. Nonresponders who experienced disease progression at 6 months or 1 year fared somewhat better, with median survivals of 15 to 19 months. Nonprogression was the best predictor of improved survival, with median survival durations of 34 and 33 months, respectively, using the 6-month and 12-month landmarks.

Evaluation of Myeloma Response in the Cox Survival Model
The myeloma response was evaluated in the Cox model as a univariate and multivariate prognostic factor in landmark models and also as a univariate and multivariate time-dependent covariate. The 6- and 12-month landmarks for progression and different categories of response were compared with the time-dependent model as summarized in Table 5. The hazard ratios and P values indicate the strong correlation between progression and OS for each model. Notice in Table 5 that >= 75% response and any response are only significant with univariate and multivariate analyses in the time-dependent model. Response by itself is either minimally significant or not significant, looking simply at the 6-month and 1-year landmarks. The Cox models confirm an interaction between response and progression, as indicated in the Kaplan-Meier curves. The interaction terms in each of the Cox models were highly significant (P < .001). These data indicate that, although response has some impact, the longer that a patient avoids PD, the better the survival duration. The underlying dominant predictor is time to progression.


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  		Table 5. Univariate and Multivariate Regression Models for Response and/or Progression

 
Correlates of time to first progression are summarized in Table 6. In essence, time to progression is correlated well with the prognostic factors typically used to predict OS, such as serum beta-2 microglobulin, serum albumin level, and platelet count. Details of prognostic factors have recently been investigated by SWOG in the development of a new SWOG staging system.18


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  		Table 6. Prognostic Correlates of Time to First Progression Multivariate Analysis

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
Authors' Disclosures of...
 REFERENCES
 
When magnitude of response is considered as a single independent variable without regard for the length of response, it is not predictive of survival duration. Despite pervasive assumptions to the contrary, this is consistent with previously published data.3-8 In retrospect, the only study indicating a relationship between serum M-protein decrement and survival duration was published in 1972 and did not assess remission duration, nor use landmark techniques.2

As was emphasized in 1975,19 M-component levels are not directly correlated with myeloma cell tumor burden. Myeloma cells have a wide range of M-component synthetic rates per cell, from 0 (nonsecretory) to very high. Some therapies can also impact M-protein synthetic rate and/or metabolism without necessarily eradicating myeloma cells. From a biologic standpoint, the major determinants of survival duration for patients with myeloma are (1) myeloma stage or tumor burden, that is, the number of cells at the start of therapy, which on a fractional basis (ie, 1 per 106 or 107 initial myeloma cells) determine the initial number of resistant myeloma cells19,20; (2) the intrinsic biology of the resistant myeloma cells, that is, the number and biologic properties, especially the growth fraction, of resistant cells remaining after a particular therapy21-27; and (3) the host factors responsible for myeloma cell growth regulation.28,29

It is therefore not surprising that the best independent indicator of survival duration is the time to develop first disease progression. If residual myeloma cells remain after induction, which is unfortunately the case even with high-dose chemotherapy with transplantation, the recurrent growth potential is indicated by the time to progression. In our analyses of these four standard-dose chemotherapy regimens used by SWOG (Figs 2 and 3), lack of progression for the remission, PR, and SD subgroups translated into a doubling of survival (34 months v 13 to 15 months median; P < .001). Conversely, the majority of patients with myeloma with ultimately poorer survival experienced disease progression within the first year (Fig 3).

Two recent European studies evaluating frontline therapy for myeloma reached the same conclusion, namely that magnitude of initial regression does not impact subsequent survival duration.30,31 The Italian study by Riccardi et al31 emphasizes the excellent survival of patients with SD (median survival, 41 months). As in the current study, the only subgroup with significantly poorer survival was the subgroup of patients with PD within the first year. The median survival for PD patients in the Italian study was 13.6 months, which is remarkably similar to our values of 13 months at the 6-month landmark and 15 months at the 1-year landmark (Fig 3). These patients with early PD using conventional therapy are identified in all these studies as candidates for new approaches to treatment. Because the identifying prognostic factors of this subgroup include higher baseline serum beta-2 microglobulin and other indicators of poorer prognosis (Table 6), it may be that single and especially tandem autologous transplantation are potential priorities in these patients. Two recent studies identify particular benefit of single autologous32 and tandem33 autologous transplantation for patients with high serum beta-2 microglobulin and resistant disease after a first transplantation, respectively.

In evaluating treatment outcome, it is also important to be aware of the survival benefit in patients with SD. This patient population is often targeted for relapse protocols and novel therapies, but actually, such patients have intrinsically good prognosis (ie, similar to remission and PR patients) and may not even need any therapy at all. Patients with SD can have residual myeloma with a 0% growth fraction24,27 and have a long plateau phase without additional therapy. The plateau level of M-protein can be 3 g/dL or greater.27 The documentation of stability with serial monitoring is more important than the actual M-protein level.

It is helpful to realize that these observations in myeloma patients are also mimicked by findings in other cancer patients. For example, in a meta-analysis of frontline therapy in colorectal cancer, initial cytoreduction per se does not impact ultimate survival duration.34

There are several implications that can be derived from the presented analyses and results. Given these findings with standard-dose therapy, time to first progression is the best measure of the impact of therapy on ultimate survival duration. Disease monitoring should focus on achievement of SD or plateau phase27 and loss of stability with development of clinically significant disease progression or relapse. Indicators of disease stability or plateau are low L1%24,27 and negative fluorodeoxyglucose positron emission tomography scan.35 Besides rather arbitrary increases in serum and/or urine M-component levels, determination of disease progression requires precise criteria of disease activation. New bone disease, reduction in hemoglobin, and other clinical parameters can be used to clearly document the need for therapy.

It will be important to assess whether these data derived from standard-dose protocols also apply to high-dose therapy with stem-cell rescue as well as biologic treatments such as thalidomide and/or bortezomib. Our results suggest that clinicians and investigators should pay less attention to the precise decrement in M-protein level and more attention to progression of disease in assessing utility and clinical benefit of standard chemotherapy regimens in multiple myeloma. Although >= 50% M-protein reduction is still a reasonable yardstick with which to assess treatment outcome, the quality and length of disease stability or plateau phase (including in the SD subgroup) are more critical. Lack of progression within 6 to 12 months is a particularly important indicator. With the advent of many new therapies for the treatment of relapsing disease, the sequential or cumulative benefit with different therapies can be assessed by documenting times to progression. The time to development of clinical relapse becomes increasingly important in assessment of quality of life, treatment toxicity, and potential overall survival benefit.


   Authors' Disclosures of Potential Conflicts of Interest
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors' Disclosures of...
REFERENCES
 
The authors indicated no potential conflicts of interest.


   NOTES
 
Authors' disclosures of potential conflicts of interest are found at the end of this article.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors' Disclosures of...
 REFERENCES
 
1. Durie BG, Bataille R: Therapeutic implications of myeloma staging. Eur J Haematol Suppl 51:111-116, 1989[Medline]

2. Alexanian R, Bonnet J, Gehan E, et al: Combination chemotherapy for multiple myeloma. Cancer 30:382-389, 1972[CrossRef][Medline]

3. Anderson JR, Cain KC, Gelber RD: Analysis of survival by tumor response. J Clin Oncol 1:710-719, 1983[Abstract]

4. Palmer M, Belch A, Brox L, et al: Are the current criteria for response useful in the management of multiple myeloma? J Clin Oncol 5:1373-1377, 1987[Abstract/Free Full Text]

5. Palmer M, Belch A, Hanson J, et al: Reassessment of the relationship between M-protein decrement and survival in multiple myeloma. Br J Cancer 59:110-112, 1989[Medline]

6. Baldini L, Radaelli F, Chiorboli O, et al: No correlation between response and survival in patients with multiple myeloma treated with vincristine, melphalan, cyclophosphamide, and prednisone. Cancer 68:62-67, 1991[CrossRef][Medline]

7. Marmont F, Levis A, Falda M, et al: Lack of correlation between objective response and death rate in multiple myeloma patients treated with oral melphalan and prednisone. Ann Oncol 2:191-195, 1991[Abstract/Free Full Text]

8. Durie BGM: Is magnitude of initial response predictive for survival in multiple myeloma? Ann Oncol 2:166, 1991[Free Full Text]

9. Crowley J, Jacobson J, Alexanian R: Standard-dose therapy for multiple myeloma: The Southwest Oncology Group Experience. Semin Hematol 38:203-208, 2001[CrossRef][Medline]

10. Salmon SE, Tesh D, Crowley JJ, et al: Chemotherapy is superior to sequential hemibody radiation for remission consolidation in multiple myeloma: A Southwest Oncology Group study. J Clin Oncol 8:1575-1584, 1990[Abstract]

11. Salmon SE, Crowley JJ, Grogan TM, et al: Combination chemotherapy, glucocorticoids, and alpha interferon in the treatment of multiple myeloma: A Southwest Oncology Group study. J Clin Oncol 12:2405-2414, 1994[Abstract/Free Full Text]

12. Salmon SE, Crowley JJ, Balcerzak SP, et al: Interferon versus interferon plus prednisone maintenance therapy for multiple myeloma: A Southwest Oncology Group study. J Clin Oncol 16:589-592, 1998[Abstract]

13. Berenson R, Crowley JJ, Grogan TM, et al: Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 99:3163-3168, 2002[Abstract/Free Full Text]

14. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958[CrossRef]

15. Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163-170, 1966[Medline]

16. Cox DR: Regression models and life-tables (with discussion). J R Stat Soc B 34:187-220, 1972

17. Crowley JJ, LeBlanc M, Jacobson JL, et al: Some exploratory tools for survival analysis: Lecture notes in statistics. Proc First Seattle Symposium Biostatistics 1:199-229, 1997

18. Jacobson JL, Hussein MA, Barlogie B, et al: A new staging system for multiple myeloma patients based on the Southwest Oncology Group (SWOG) experience. Br J Haematol 122:441-450, 2003[CrossRef][Medline]

19. Durie BGM, Salmon SE: A clinical staging system for multiple myeloma. Cancer 36:842-854, 1975[CrossRef][Medline]

20. Skipper HE: Thoughts on cancer chemotherapy and combination modality therapy. JAMA 230:1033-1035, 1974[Abstract/Free Full Text]

21. Hofmann V, Salmon SE, Durie BGM: Drug resistance in multiple myeloma associated with high in vitro incorporation of 3[H]-Thymidine. Blood 58:471-476, 1981[Abstract/Free Full Text]

22. Durie BGM, Young LA, Simon SE: Human myeloma in vitro colony growth: Interrelationships between drug sensitivity, cell kinetics and patient survival duration. Blood 61:929-934, 1983[Abstract/Free Full Text]

23. Durie BGM: Is myeloma really a monoclonal disease? Br J Haematol 57:357-363, 1984[Medline]

24. Boccadoro M, Gavarotti P, Fossati G, et al: Low plasma cell 3(H) thymidine incorporation in monoclonal gammopathy of undetermined significance (MGUS) smoldering myeloma and remission phase myeloma: A reliable indicator of patients not requiring therapy. Br J Haematol 58:689-696, 1984[Medline]

25. Durie BGM, Vela E, Baum V, et al: Establishment of two new myeloma cell lines from bilateral pleural effusions: Evidence for sequential in vivo clonal change. Blood 66:548-555, 1985[Abstract/Free Full Text]

26. Durie BGM, Grogan TM: CALLA-positive myeloma: An aggressive subtype with poor survival. Blood 66:229-232, 1985[Abstract/Free Full Text]

27. Durie BGM, Russell DH, Salmon SE: Reappraisal of plateau phase in myeloma. Lancet 2:65-68, 1980[CrossRef][Medline]

28. Brown RD, Pope B, Yuen E, et al: The expression of T cell related costimulatory molecules in multiple myeloma. Leuk Lymphoma 31:379-384, 1998[Medline]

29. Brown RD, Pope B, Murray A, et al: Dendritic cells from patients with myeloma are numerically normal, but functionally defective as they fail to up regulate CD80 (B7–1) expression after huCD40LT stimulation due to inhibition by transforming growth factor-beta1 and interleukin-10. Blood 98:2992-2998, 2001[Abstract/Free Full Text]

30. Oivanen TM, Kellokumpu-Lehtinen P, Koivisto AM, et al: Response level and survival after conventional chemotherapy for multiple myeloma: A Finnish Leukaemia Group study. Eur J Haematol 62:109-116, 1999[Medline]

31. Riccardi A, Mora O, Tinelli C, 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 39:1:31-37, 2003

32. Morgan G, Davies F, Hawkins K, et al: The MRC myeloma VII trial of standard versus intensive treatment in patients < 65 years of age with multiple myeloma. N Engl J Med 348:1875-1883, 2003[Abstract/Free Full Text]

33. Attal M, Harousseau JL, Facon T, et al: Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 26:2495-2502, 2003

34. Buyse M, Thirion RW, Carlson T: Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: A meta-analysis—Meta-Analysis Group in Cancer. Lancet 356:373-378, 2000[CrossRef][Medline]

35. Durie BGM, Waxman A, D'Agnolo A, et al: Whole body FDG/PET scanning identifies high risk myeloma. J Nucl Med 43:1457-1463, 2002[Abstract/Free Full Text]

Submitted May 15, 2003; accepted November 2, 2003.


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M. A. Hussein, R. Baz, G. Srkalovic, N. Agrawal, R. Suppiah, E. Hsi, S. Andresen, M. A. Karam, J. Reed, B. Faiman, et al.
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R. C. Kane, A. T. Farrell, R. Sridhara, and R. Pazdur
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C. A. Huff, W. Matsui, B. D. Smith, and R. J. Jones
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R. Baz, L. Li, K. Kottke-Marchant, G. Srkalovic, B. McGowan, E. Yiannaki, M. A. Karam, B. Faiman, R. A. Jawde, S. Andresen, et al.
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