Individualized chemotherapy in multiple myeloma by cytostatic drug sensitivity testing of colony-forming stem cells.

Chemotherapy for patients with multiple myeloma was individually selected on the basis of antiproliferative drug sensitivity determined in vitro by a clonogenic assay. Myeloma stem cells were preincubated with various cytostatic drugs and allowed to form colonies in a plasma clot culture system. In 21 out of 24 prospective trials on 14 patients, clinical improvement corresponded to the cytostatic drug sensitivity determined in vitro amounting to a predictive accuracy of 87.5% for the test system. Repeated cytostatic drug sensitivity testing in five untreated patients and in seven patients under intensive chemotherapy during the test intervals indicated the emergence of resistant tumor cell clones in both groups, but the loss of sensitivity was much more pronounced in the cells of patients receiving therapy. Selection of cytostatic drugs according to the results of in vitro antiproliferative drug sensitivity testing of myeloma stem cells should improve the efficacy of subsequent chemotherapy. Furthermore, the surveillance of evolving tumor cell clones by periodical reevaluation of the patient's sensitivity status may add a new dimension to the treatment regimens for multiple myeloma.