Abstract
The results of the MRC Myeloma VII trial and overview analysis of comparable trials have suggested that VAD-like induction chemotherapy followed by high dose therapy (HDT) with autologous transplantation may be regarded as a new standard treatment for multiple myeloma. However, there is a need for data from the extended follow up of patients in such trials to provide confirmatory evidence of the benefit of treatment incorporating HDT compared with conventional dose treatment, in particular to determine the long term difference in survival and the impact of attaining a complete response (CR) following intensive treatment. We present an updated analysis of Myeloma VII with median follow up of 5.5 years. Myeloma VII is the largest trial of its type in which patients with previously untreated multiple myeloma, age <65 years, were randomized to receive either standard conventional-dose combination chemotherapy (ABCM) or a sequence of treatment, C-VAMP followed by high dose therapy (HDT), typically melphalan 200g/m2 with autologous stem cell transplant. The planned maintenance in both arms was interferon α-2a. The trial, initiated in 1993 and closed to entry in 2000 and was conducted to MRC guidelines for good clinical practice in clinical trials. In the 401 evaluable patients the CR rate was 44% in the intensive therapy group, 8% in the standard therapy group (p<0.001). Intention to treat analysis showed a survival benefit of 14.1 months in the intensive arm (Figure 1); median 56.3 months (95% CI 46.0–74.6) vs. 42.2 months (95% CI 33.1–48.9), p=0.004 (log rank test). Progression free survival was also improved in the intensive group, median 31.2 months (95% CI 27.1–37.5) compared with 19.5 months (95% CI 16.2–21.6) in the standard group (p=<0.001). This analysis provides confirmatory evidence that treatment including high dose therapy is superior to conventional dose chemotherapy. Long term follow up of this study shows that the benefits of intensive treatment are maintained long term and that an important therapeutic aim is the achievement of CR. For the patients receiving the full protocol, the differences are accentuated, implying that maximising numbers of patients getting to transplant is an important therapeutic aim. These results would also support the continuing development of peri-HDT strategies to further improve outcomes.
Figure Figure
Long-term follow-up after high-dose therapy for high-risk multiple myeloma
