Kyle RA. "Benign" monoclonal gammopathies
after 20 to 35 years of follow-up. Mayo Clin Proc. 1993;68:26-36.
In patients with an apparently benign monoclonal
gammopathy, follow-up must be continued indefinitely because multiple myeloma,
amyloidosis, macroglobulinemia, or related disorders occur in approximately
a fourth of them.
Klein, B, Zhang XG, Lu ZY,
et al. Interleukin-6 in human multiple myeloma. Blood. 1995;85:863-872.
IL-6 is involved in the proliferation of normal plasmablastic
cells and in their differentiation into mature plasma cells. It is a major
growth factor for myeloma cells in vitro and is likely to be a myeloma
cell growth factor in vivo.
Demartis A, Bernassola F, Savino
R, et al. Interleukin-6 receptor superantagonists are potent inducers of
human multiple myeloma cell death. Cancer Res. 1996;56: 4213-4218.
IL-6 receptor antagonists are pro-apoptotic factors
for the IL-6-dependent human myeloma cell line XG-1. Their capacity to
induce cell death is directly related to their affinity for IL-6R alpha,
the degree of gp130-binding impairment, and their efficiency to inhibit
intracellular signaling events.
Dinarello CA. Biologic basis
for interleukin-1 in disease. Blood. 1996;87:2095-2147.
Interleukin-1 (IL-1a
and IL-1b) is the prototypic
"multifunctional" cytokine. Unlike the lymphocyte and colony-stimulating
growth factors, IL-1 affects nearly every cell type and often in concert
with other cytokines or small mediator molecules. Although some lymphocyte
and colony-stimulating growth factors may be therapeutically useful, IL-1
is a high inflammatory cytokine, and the margin between clinical benefit
and unacceptable toxicity in humans is narrow.
Oken MM, Harrington DP, Abramson
N et al. Comparison of melphalan and prednisone with vincristine, carmustine,
melphalan, cyclophosphamide, and prednisone in the treatment of multiple
myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer.
1997; 79:1561-1567.
VBMCP is more effective than MP in producing and
sustaining remission of multiple myeloma. For patients who can tolerate
moderately intensive combination chemotherapy, VBMCP is associated with
a marginal survival advantage and an apparently greater chance of surviving
five years.
Salmon SE, Crowley JJ, Grogan
TM, et al. Combination chemotherapy, glucocorticoids, and interferon alfa
in the treatment of multiple myeloma: a Southwest Oncology Group study.
J Clin Oncol. 1994; 12:2405-2414.
Higher-dose glucocorticoids increase frequency of
response to chemotherapy and prolong survival in myeloma. Interferon maintenance
with the dose schedule used in this trial did not prolong relapse-free
or overall survival.
Dalton WS. Anemia in multiple
myeloma and its management. Cancer Control: JMCC. 1998;5 (suppl
2):46-50.
Myeloma patients who have a hemoglobin level of less
than 11 g/dL may benefit from the use of rHuEpo. Those with normal serum
erythropoietin levels may need a higher dose of rHuEpo to obtain a response
compared to patients with low levels of erythropoietin.
Berenson JR, Lichtenstein A,
Porter L, et al. Long-term pamidronate treatment of advanced multiple
myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J
Clin Oncol. 1998;16:593-602.
Long-term monthly infusions of pamidronate as an
adjunct to chemotherapy are superior to chemotherapy alone in reducing
skeletal events in stage III multiple myeloma patients and may improve
the survival of patients on salvage therapy.
Salmon SE, Crowley JJ, Balcerzak
SP, et al. Interferon versus interferon plus prednisone remission maintenance
therapy for multiple myeloma: a Southwest Oncology Group Study. J Clin
Oncol. 1998;16:890-896.
Interferon plus prednisone (IFN/P) was more effective
than IFN alone. Improved relapse-free survival may be attributable to IFN/P
or to the use of prednisone for maintenance. This latter alternative is
currently being studied.
Attal M, Harousseau JL, Stoppa
AM, et al. High-dose therapy in multiple myeloma: an updated analysis of
the IFM 90 protocol. Blood. 1997;90 (suppl 1 pt 1):1858. Abstract.
This new analysis of the IFM 90 trial confirmed that
high-dose therapy improves response rate, event-free survival, and overall
survival in multiple myeloma. However, the six-year postdiagnosis probability
of event-free survival after high-dose therapy (24%) has to be improved
in future trials.