Improved survival of increased-risk myeloma patients on combined triple- alkylating-agent therapy: a study of the CALGB

Abstract

Two hundred fifty-two previously untreated evaluable patients with multiple myeloma were entered into a study testing a regimen of three intravenous alkylating agents, melphalan, cyclophosphamide, and carmustine (BCNU), given in combination (BCMP) against a regimen employing oral melphalan (MP). Both regimens included a tapering course of prednisone. Objective responses based on the Myeloma Task Force criteria were significantly more frequent in the group receiving BCMP. Survival for the entire group of BCMP-treated patients was not significantly better than that for MP-treated patients (p = 0.62). However, when the survival of the poor-risk (high tumor cell load) group of patients treated with BCMP was compared with the survival of the poor-risk (high tumor cell load) group of patients treated with MP, an improvement in survival attributable to BCMP therapy was seen (p = 0.049 and 0.02, respectively). In the good-risk (low and intermediate tumor cell load) group, BCMP treatment resulted in a trend toward poorer survival, but this did not achieve statistical significance (p = 0.080 and 0.23, respectively). These results indicate that optimal therapy in myeloma may be dependent on the extent of disease at the time of first treatment. Additional studies to explore the effects of treatment intensity and duration are needed in order to design improved myeloma treatment based on the patient's extent of disease.

Human myeloma cell apoptosis induced by interferon‐α

“…Multiple myeloma remains an incurable haematological malignancy characterized by various clinical manifestations such as hyperproteinaemia, renal dysfunction, bone lesions and immunodeficiency ( Oken, 1997; Bjorkstrand, 1996). Since the introduction of melphalan and prednisone (MP therapy) to improve the clinical response to multiple myeloma, large numbers of multi‐drug chemotherapies including vinca alkaloids, anthracyclines and nitrosoureas have been reported ( Case et al , 1977 ; Harley et al , 1979 ; Salmon et al , 1983 ; MacLennan et al , 1988 ). However, there has been little improvement in outcome during the past three decades ( Oken, 1997; Bjorkstrand, 1996).…”

Corticosteroid is not beneficial in multiple‐drug combination chemotherapy for multiple myeloma

“…Combination chemotherapy has resulted in higher response rates than the standard melphalanprednisone in the treatment of multiple myeloma. At the time of planning the present study the higher response rates seemed to translate into prolonged survival times (3,7). There were, however, no data as to whether combination schedules also contained drugs that did not contribute to the result of the treatment or that were even harmful.…”

Aggressive combination chemotherapy in multiple myeloma. A multicentre trial

“…The report of Case et a1 (1) on their results of the application of the M-2 protocol was the first indication that an aggressive combination chemotherapy might be beneficial in the treatment of multiple myeloma. Some other trials on combination chemotherapy in myeloma were disappointing, and serious criticism appeared of the report of Case et al (2,3,10), cast doubt on the validity of their results and the role of vincristine in the combination. The total response rate (78%) in our multicentre trial is, however, in the same order as the reported response rates using M-2 in single-centre studies (87% and 78%, 1, ll), and the survival time among our patients from the initiation of the treatment is similar to that reported by Paccagnella et a1 (1 1) and Tirelli et a1 (12), and similar to the survial time of the patients of Case et a1 (1) from the diagnosis of myeloma.…”