Background: High dose therapy with autologous stem cell transplantation (HDT-ASCT) has prolonged survival in patients with multiple myeloma. Patients who achieve a complete response (CR) benefit the most from this form of therapy. Thus, achieving a CR is an important goal of therapy and it will be beneficial if the probability of achieving CR can be determined for any patient before transplant.

Patients and Methods: A large cohort of patients with myeloma who received HDT-ASCT at Mayo Clinic Rochester was studied. The impact of various demographic, clinical and laboratory characteristics relating to the patients and their disease acquired were studied for their impact on response to HDT-ASCT, especially CR. Patients with a serum M-protein <0.1g/dL were excluded. Response definitions were as defined by established criteria. Survival analysis was performed according to the Kaplan-Meier method while univariate and multivariate analyses were performed with the proportional hazards method. We utilized knowledge of the rate of M-protein production by myeloma cells together with the clearance of the protein to estimate the pre-transplant disease burden.

Results: We studied 224 patients with a median age of 56.5 years (32.6 – 71). Patients were transplanted a median of 8.7 months after diagnosis. Almost all patients had a response to HDT-ASCT and 78 (35%) achieved a CR. Those patients who achieved a CR had a longer time to progression (TTP) compared to those who did not achieve CR (Figure 1). The cohort was thus divided into two groups: patients who achieved CR and those that did not. The clinical and laboratory characteristics of the two groups were compared. Among the pre-transplant parameters tested, only the size of the serum M-spike was a predictor for CR (p<0.0001). A simple function that describes the probability of achieving CR based on the serum M-spike before HDT-ASCT is described. The estimated rate of tumor re-growth after HDT-ASCT in patients who obtain a CR and in patients who only get a partial response are presented.

Conclusions: The pre-transplant disease burden in myeloma is the main determinant of response to HDT-ASCT. The individual probability of achieving CR can be estimated from simple clinical parameters providing a quantitative risk assessment prior to such a high-risk procedure. There is significant expansion of myeloma cells after HDT-ASCT. The design of clinical trials may benefit from knowledge of the kinetic aspects of the disease.

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Topics:
m-spike, multiple myeloma, transplantation, autologous stem cell transplant, complete remission, neoplasms, partial response, time to progression, treatment goals, kaplan-meier survival curve

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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