(Southwest Oncology Group [SWOG] Phase 111 myeloma study 8229/30), in which the prognostic significance of pretreatment serum 8, microglobulin levels ...
Prognostic Value of Pretreatment Serum /3* Microglobulin in Myeloma: A Southwest Oncology Group Study By Brian G.M. Durie, Donna Stock-Novack, Sydney E. Salmon, Paul Finley, Jean Beckord, John Crowley, and Charles A. Coltman Six hundred twelve eligible, previously untreated patients with active multiple myeloma and at least some data available for analysis were entered into a randomized trial (Southwest Oncology Group [SWOG] Phase 111 myeloma study 8229/30),in which the prognostic significance of pretreatment serum 8, microglobulin levels was evaluated. Because there was no statistically significant survival difference between the alternating and syncopating VMCP/ VBAP regimens, it was possible t o evaluate serum 8, microglobulin for the total population all together. The serum 8, microglobulin measurementsshowed the highest significance of any prognostic factor, both in the bivariate and multivariate regression analyses. The median survival was 36 months for the 322 patients with pretreatment serum 8, microglobulin values of t6 pg/mL, as compared with a median survival of 23 months for the 225 patients
with a 8, level of 26 mcg/mL ( P < .OOOl). The stepwise multiple regression model first contained serum 8, microglobulin, followed by serum albumin, serum calcium, age. and serum creatinine. Serum 8, microglobulin was highly correlated with stage: median values ranged from 3.7 pg/mL for stage IA, t o 10.1 for stage 1118. It was possible t o stratify myeloma patients based on combinations of serum 8, microglobulin with both albumin and age, producing excellent separation of patients into low-, intermediate-, and high-risk categories. It is concluded that serum 8, microglobulin is the most powerful prognostic factor currently available for multiple myeloma and that it can be used alone or in combination with other variables for pretreatment stratification. 0 1990 by The American Society of Hematology.
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lesions (scaled as previously described’), percentage of plasma cells in the bone marrow, and other basic pretreatment parameters such as liver function tests and electrolytes were also assessed.
REVIOUS REPORTS documented the usefulness of serum & microglobulin levels for predicting survival duration in patients with multiple Despite the many positive reports of the utility of serum p2 microglobulin determinations, some investigatorsquestioned the role of this marker in the management of multiple myeloma.’ With recognition of this ongoing controversy, a prospective Southwest Oncology Group (SWOG) Study was initiated to evaluate serum B2 microglobulin measurements. Pretreatment serum specimens were sent to a central testing laboratory (at the University of Arizona, Tucson), and results were correlated with other pretreatment prognostic factors, with response to treatment and subsequent survival duration. This report outlines the detailed statistical analyses performed, which indicate the considerable prognostic importance of serum p2 microglobulin measurements, both alone and combined with serum albumin, age, and other parameters. Useful stratification or staging systems incorporating serum p2 microglobulin, serum albumin, and age are presented. MATERIALS AND METHODS
Between 1982 and 1987,621 patients were entered on the SWOG myeloma protocol 8229130. Six hundred twelve of these patients proved to be eligible for the study and had some data available at the time of analysis. There are fewer patients in some analyses due to missing data. For example, 547 patients had values of serum fi2 microglobulin (see Table 2). The patients were randomized to receive alternating chemotherapy consisting of vincristine, melphaIan, cyclophosphamide, prednisone (VMCP)/vincristine, BCNU, adriamycin (VBAP), administered either using a one to one alternation or a three to three alternation. The exact details of the chemotherapy schedule were previously published.’ A complete inventory of the presenting clinical and laboratory features of all patients entered on to study was collated. The inventory included such basic parameters as age (at time of registration), race, sex, performance status, myeloma stage (Durie-Salmon method’), immunoglobulin (Ig) heavy chain type, Ig light chain type, hemoglobin, hematocrit, white blood cell count, platelet count, serum calcium, serum albumin, serum creatinine, serum uric acid, serum and/or urinary monoclonal component levels in grams per deciliter in the serum, or grams per day in the urine. Polyclonal Ig levels, the extent of bone Blood, Vol 75, No 4 (February 15), 1990: pp 823-830
Evaluation of Serum
& Microglobulin
Serum fiz microglobulin levels were measured in the Clinical Pathology Department at the University of Arizona (Paul Finley), with a radioimmunoassay using the Phadebas & microtest technique (Pharmacia Diagnostics, Uppsala, Sweden). Initial test kits for this study were supplied by Pharmacia free of charge (see Acknowledgment). Corrections were not used for renal function in the calculation of the serum fi2 microglobulin levels used for analysis. Loglo values were calculated as previously reported!.’ Statistical Methods
Extensive evaluation of models was performed to determine the important prognostic variables for survival duration and response to From the Departments of Medicine and Pathology. University of Arizona, and the Arizona Cancer Center, Tucson; the Southwest Oncology Group Statistical Center, Seattle, WA; and the University of Texas, Health Science Center, San Antonio. Submitted February 10.1989: accepted September 25,1989. Supported in part by the following PHS Cooperative Agreement Grant numbers awarded by the National Cancer Institute, DHHS: CA-13612, CA-37429, CA-20319, CA-37981, CA-22433, CA28862, CA-13238, CA-04919, CA-04915, CA-16385, CA-35261, CA-03389, CA-35090, CA-22411. CA-04920, CA-35128, CA1221 3, CA-35117, CA-35431, CA-36020, CA-12644, CA-46113, CA-14028. CA-37445, CA-35274. CA-27057, CA-35438, CA35995, CA-35176, CA-35438. CA-32734, CA-03096, CA-46136, CA-35178, CA-35996, CA-35262. CA-35119. CA-35158. CA35084, CA-35429, CA-35192, CA-32102. Address reprint requests to Southwest Oncology Group (SWOG8229130). Operations Ofice. 5430 Fredericksburg Rd, Suite #618. San Antonio, TX 78229-6197. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C.section 1734 solely to indicate this fact. 8 1990 by The American Society of Hematology. 0006-4971/90/7503-O015$3.00/0 823
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DURlE ET AL Table 1. Survival and Pretreatment: Serum 8, MicroglobulinWith Different Cutoff Values 4d m L Serum & Microglobulin Cutoff Value
Patient No.
>cutoff
