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Plasmablastic Morphology An Independent Prognostic Factor With
Clinical and Laboratory Correlates: Eastern Cooperative Oncology
Group (ECOG) Myeloma Trial E9486 Report by the ECOG Myeloma Laboratory
Group
Philip R. Greipp,
Traci Leong,
John M. Bennett,
Jean P. Gaillard,
Bernard Klein,
James A. Stewart,
Martin M. Oken,
Neil E. Kay,
Brian Van Ness, and
Robert A. Kyle
From the Mayo Clinic, Rochester, MN; Dana Farber Cancer Institute,
Boston, MA; the University of Rochester, Rochester, NY; the University
of Nantes, Nantes, France; the University of Wisconsin, Madison;
Virginia Piper Cancer Institute, Minneapolis, MN; the University of
Kentucky, Lexington; and the University of Minnesota, Minneapolis.
We studied the prognostic significance of plasmablastic (PB)
multiple myeloma (MM) in Eastern Cooperative Oncology Group Phase III
trial E9486. Two reviewers independently reviewed 453 cases. They
agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85%
concordance (P < .0001). These PB cases had significantly lower hemoglobin and serum albumin levels, higher calcium and  2-microglobuin levels, and higher percentage BM plasma cells (PC) by
immunofluorescence. They had higher bone marrow PC labeling indices,
higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a
higher probability of ras mutations. Three treatment regimens
were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan,
cyclophosphamide, and prednisone (VBMCP) alone; VBMCP with
added cyclophosphamide (HiCy); or recombinant interferon  2 (rIFN2). Although the numbers are low, patients
with PB had a significantly lower response rate versus non-PB MM when
treated with VBMCP (treated, 47.1% v nontreated, 66.5%
[P = .015]). Patients with nonresponding PB had a
significantly higher progression rate than non-PB cases (30.6%
v 11.8% [P < .0001]), especially with VBMCP
alone (35.3% v 15.8% [P = .002]), and with
added HiCy (37.5% v 9.8% [P < .0001]), but not
with added rIFN2. Event-free and overall survival of PB MM was
shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no
survival difference between the patients who were classified as PB by
both reviewers versus patients classified as PB by only one reviewer.
We conclude that PB MM is a discrete entity associated with more
aggressive disease and shortened survival. Tumor cell ras
mutations and increased sIL-6R may contribute to a higher proliferation
rate and reduced survival. There were significant improvements in
response and progression with the addition of HiCy and rIFN2 to
VBMCP, but the numbers were small and improved survival could not be
shown.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2501-2507
© 1998 by The American Society of Hematology.
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