Prednisone Myeloma Remission Maintenance
July 1, 2002
Prednisone Myeloma Remission Maintenance
Abstract & Commentary
Synopsis: Maintenance of remission in patients with multiple myeloma who have responded to initial chemotherapy remains controversial, inasmuch as clinical trials to date have demonstrated only modest effects, particularly on overall survival. In this report from the Southwest Oncology Group, the use of prednisone administered on alternate days at a dose of 50 mg was shown to significantly enhance progression free and overall survival when compared to prednisone administered at a lower dose (10 mg). Although confirmatory studies would be of value, this approach is both well tolerated and inexpensive and, thus, likely to be adapted rapidly in various clinical settings.
Source: Berenson JR, et al. Blood. 2002;99:3163-3168.For the 50% of treated patients with myeloma who achieve objective markers of remission, controversy remains regarding the value of maintenance therapy. Interferon has been shown to prolong remission by several months, but improvement in overall survival has been difficult to demonstrate.1-3 The current report details findings from the Southwest Oncology Group (SWOG) study 9210 in which patients who achieved remission after either vincristine, adriamycin, decadron + prednisone (VAD-P) or vincristine, adriamycin, decadron, prednisone, and quinine (VAD-P/Q) were randomized to receive alternate-day prednisone, either at a low dose (10 mg) or a high dose (50 mg).
Of the 126 patients who achieved at least a partial remission with initial therapy (25% reduction tumor reduction), 65 were randomized to receive the 10-mg prednisone maintenance dose and 61 were randomized to receive the 50-mg dose. The median progression-free survival was significantly improved in the high-dose prednisone arm compared with the low-dose arm (14 months vs 5 months; P =.003) with a median follow-up for living patients of 44 months from randomization to maintenance therapy. Median overall survival from maintenance randomization was also significantly prolonged in the high-dose group (37 months vs 26 months; P = .05).
Comment by William B. Ershler, MD
Interferon alone has been reported to prolong remission in myeloma, but the findings have been modest and it remains to be demonstrated that overall survival is enhanced.1-3 However, the addition of corticosteroids to interferon has recently been shown to be effective maintenance therapy, including overall survival,4,5 and, hence, there was rationale to examine the effects of corticosteroids alone as maintenance therapy. Furthermore, corticosteroids are known to inhibit the transcription activator NF-kB which might result in myeloma cell apoptosis as well as a reduction in expression of interleukins 6 and 1b, both of which are stimulatory to plasma cell proliferation as well as osteoclast activation and resultant lytic bone destruction.
The current study clearly demonstrated that pharmacological doses (50 mg) of prednisone administered on alternate days was both safe and effective in prolonging progression-free and overall survival. Furthermore, there was little toxicity observed, although a thorough examination of bone mineral content and density was not undertaken. Certainly, with periodic administration of bisphosphonates (eg, pamidronate or zoledronate), it would seem likely that the continuation of alternate-day prednisone would be both safe and effective in the continued management of patients with myeloma who responded to initial cyclical chemotherapy. Thalidomide might also be useful in this setting; and it would seem appropriate to compare in clinical trial the use of this drug (which also is reported to inhibit key proinflammatory cytokines, as well as inhibit angiogenesis) with prednisone, either alone or in combination.
Dr. Ershler of INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.
References
1. Mandelli F, et al. N Engl J Med. 1990;20:1430-1434.
2. Salmon SE, et al. J Clin Oncol. 1994;12:2405-2412.
3. Peest D, et al. Eur J Cancer. 1995;31A:146-150.
4. Palumbo A, et al. Acta Haematol. 1993;90:71-76.
5. Salmon SE, et al. J Clin Oncol. 1998;16:890-896.
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