Response level and survival after conventional chemotherapy for multiple myeloma: a Finnish Leukaemia Group study.

The relation between overall survival time (OS) and response level (CR, 75%R, PR, MR, SD) was analysed in 432 multiple myeloma patients from 4 prospective Finnish Leukaemia group trials, treated with conventional chemotherapy. The primary regimen was either melphalan and prednisolone or combination chemotherapy with melphalan as a main component. Both the influence of the pre-treatment factors in patients with different levels of responses and the aspects related to chemotherapy were analysed. The 324 patients aged up to 70 yr and the 10(8) older patients were dealt with as separate groups. Irrespective of the primary chemotherapy regimen, the level of response was not significantly influencing in the OS time, and this was true in both age categories. The median OS of the patients up to 70 yr of age who had any response was 57 months, compared to the 10 months of those with PD (p < 0.001). The corresponding figures for the older patients were 40 and 4 months (p <0.001), respectively. The pretreatment prognosticators for the patients with minimal responses were not more favourable than for patients with responses at higher levels. The prolonged primary chemotherapy was favourable in patients having responses less than PR. Accordingly, the primary goal of conventional chemotherapy for multiple myeloma is stabilization of disease, not the level of response.

Prognostic value of serum M-protein doubling time at escape from plateau of multiple myeloma. The Finnish Leukaemia Group.

A long plateau phase is one of the strongest signs predicting long survival in multiple myeloma. The kinetics of escape from the plateau is, however, poorly known, and so is its influence on subsequent survival. During a 9-yr follow-up of 432 myeloma patients the serum M-protein doubling time at first relapse was measured from serial observations in 137 cases. Univariate and multivariate analyses of pretreatment characteristics and of characteristics associated with chemotherapy were used to identify the predictors influencing on M-protein doubling time. In 65 patients the M-protein doubling time was 6 months or less and in 72 longer, with median remaining survival times of 17 and 45 months, respectively; 50% of the former group had any response to salvage chemotherapy, compared to 75% of the latter group. In univariate analysis stage and Hb were significant predictors for the M-protein doubling time. An at least 75% response was associated with short doubling time. However, the multivariate analysis left only a long preceding plateau and use of several drug combinations during primary chemotherapy as significant predictors for a long M-protein doubling time. A M-protein doubling time of 6 months or less is associated with frequent resistance to salvage chemotherapy and short remaining survival. A short doubling of the M-protein is preceded by a short plateau. The use of several drug combinations during primary chemotherapy does not jeopardize the later course of the disease. A short M-protein doubling time seems not be a chemotherapy induced phenomenon.

Plateau phase in multiple myeloma: an analysis of long-term follow-up of 432 patients. Finnish Leukaemia Group.

DAta from an 8-year follow-up of 432 myeloma patients were analysed for incidence, duration and prognostic value of plateau phase and factors favouring its achievement. The first-line chemotherapy was melphalan and prednisolone in 121 cases, combination chemotherapy in 311 cases. The survival times were similar despite different response rates. Any response resulted in survival significantly (P<0.001) better than in patients with progressive disease, but the level of response had no influence in this respect. A plateau of at least 3 months was achieved in 81%, at least 6 months in 74%, at least 12 months in 59% and at least 24 months in 33%. Groups with significantly different (P<0.001) survivals were identified: a plateau of <3 months, 3-11 months, 12-23 months, and 24 months or longer, with median survivals of 10, 27, 46 and 81 months, respectively. In the multivariate analysis of pretreatment variables, only haemoglobin (Hb) (P<0.001) and creatinine at 2 months (P<0.01) were significant for a plateau >12 months. After inclusion of chemotherapy data, Hb and time taken to reach the best response were still significant (P=0.002). The predictive power of high Hb and slow response for achieving a plateau of 6 or 12 months was 79%. Accordingly, the criteria for response of treatment for multiple myeloma should include a stable period of at least 3 months; the criteria for a plateau a stable period of at least 12 months in order to have real prognostic significance.