Time to First Progression, but Not Β2-Microglobulin, Predicts Outcome in Myeloma Patients Who Received Thalidomide as Salvage Therapy.

Survival for patients with multiple myeloma varies from less than 6 months to longer than 10 years. Several clinical and laboratory parameters have been described as independent predictors of survival and could help to select patients who may most benefit from different therapies. Thalidomide may have the ability to change the course of the disease or be active in patients who failed previous lines of therapies. In the present study, we evaluated baseline demographic and clinical parameters to determine their value in predicting outcome of relapsed or refractory patients treated with Thalidomide and Dexamethasone (TD). Of 138 enrolled patients (median age 61 years), 59% were treated at diagnosis with autologous transplantation and 41% with conventional chemotherapy. Patients agreed to use contraception, and women of childbearing age had a pregnancy test before enrolment. Exclusion criteria were a second malignancy, psychiatric disease and any grade 2 peripheral neuropathy. Abnormal cardiac function, chronic respiratory disease, abnormal liver or renal functions were not considered criteria for exclusion. The study was approved by the local Institutional Review Board. Written informed consent was obtained on study entry in accordance with the Declaration of Helsinki. Thalidomide was administered at 100 mg/day continuously and Dexamethasone at 40 mg/day on days 1–4 each month. Several parameters such as serum β2-microglobulin, serum C-reactive protein, IgA isotype, haemoglobin, stage, bone marrow plasmacytosis, age, serum creatinine, gender, stem cell transplantation at diagnosis, and time to first progression were analyzed in association with response rate, event-free survival (EFS) and overall survival (OS). No factor was associated with response rate by both univariate and multivariate analyses. The EFS from start of TD therapy and OS from diagnosis were 13.1 months and 74.9 months, respectively. By univariate analysis, clinical factors predictive of shorter EFS from start of TD were age younger than 65 years (p=0.04), autologous transplantation at diagnosis (p=0.02) and stage III (p=0.02). By multivariate analysis, factors associated with shorter EFS, after TD treatment, were age 65 years or younger (p=0.03), autologous stem cell transplantation at diagnosis (p=0.03) and time to first progression ≤ 12 months (p<0.05). Age ≥ 65 years (p=0.04), haemoglobin ≤ 10 g/dL (p=0.002), creatinine ≥ 2 mg/dL (p=0.05), stage III (p=0.05) and time to first progression ≤ 12 (p<0.0001) were associated with shorter OS. Factors that remained significantly associated with shorter OS in multivariate models were haemoglobin ≤ 10 g/dL (p=0.009) and time to first progression ≤ 12 months (p<0.0001). Serum elevated β2-microglobulin and C-reactive protein, generally considered poor prognostic factors, were not predictive of poor EFS or OS. Time to first progression > 12 months was the best indicator of survival. Interestingly, younger age and transplant at diagnosis negatively affect EFS but not OS from the start of TD.