Improved survival in myeloma patients: starting to close in on the gap between elderly patients and a matched normal population.

The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2·8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4·9 years) compared to conventional treatment (2·3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6·9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.

Comparison of algorithms for oral busulphan area under the concentration-time curve limited sampling estimate.

BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring (TDM) of the first dose of busulphan during conditioning prior to allogeneic stem cell transplantation provides the possibility of improving the clinical outcome via dose adjustment of subsequent doses. The plasma area under the concentration-time curve (AUC) for busulphan is generally accepted as the parameter that gives the best exposure estimate; however, the sampling frequency needed for reliable AUC calculation remains controversial. The aim of the present investigation was to develop and evaluate a limited sampling model for oral busulphan. METHODS: We have compared models using three to four samples with standard WinNonlin(®) adaptive compartment modeling based on eight samples as reference. The evaluated study population included both adult and pediatric patients, but the linear model was devised using analysis of only pediatric patient plasma concentrations. The present model was developed using data from 23 patients with a mean age of 38 years (range 13-59 years) and was evaluated in 20 pediatric patients with a mean age of 6 years (range 0.1-13 years) as well as 23 adult patients (mean age 43 years; range 18-67 years). RESULTS: In 23 patients, the mean AUC from a curve fitting model (Purves method) and a single compartment model had an intraclass correlation coefficient (ICC) of 0.947. From a log-log plot of AUC values it was evident that using this estimate of the AUC would affect dose adjustment decisions for very few of the patients. Applying the linear model using three samples resulted in an ICC of 0.932, mostly due to worse performance in the adult population. CONCLUSIONS: The present results support the use of limited sampling in clinical TDM for oral busulphan provided adequate algorithms and sampling times are used. Moreover, they also demonstrate the caution that is needed when transferring a pharmacokinetic model from a pediatric population to an adult population.