S-PHASE INDUCTION BY INTERLEUKIN-6 FOLLOWED BY CHEMOTHERAPY IN PATIENTS WITH REFRACTORY MULTIPLE-MYELOMA

The plasma cell labeling index (PCLI) in patients with multiple myelom a (MM) is relatively low and this has been associated with the low rat e of remission following chemotherapy. Interleukin-6 (IL-6) has been d emonstrated to be a major growth factor of myeloma cells. In order to increase the S-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemother apy to 15 myeloma patients with refractory disease. A total of 25 trea tment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10.0 mu g/kg (n = 6) by s ubcutaneous injection once daily for 5 days and chemotherapy was admin istered on the last day of rhIL-6 injection. The effect of rhIL-6 trea tment on labeling index (LI) was heterogeneous, but no statistically s ignificant change was noted for this particular group as a whole. In t wo patients an increase (mean 7.7%) in LI of mononuclear bone marrow c ells during the rhIL-6 treatment was demonstrated and in one patient a decrease of 2.8% was seen. Assessment of PCLI demonstrated an increas e of 2.9% in one out of six patients and a decrease of 1.9% in one out of six patients. None of the 15 patients achieved remission according to standard criteria. During the rhIL-6 treatment, 14 of the 15 patie nts developed mild constitutional adverse events (AE) well known in pa tients treated with IL-6, and none of the AE in the subsequent chemoth erapy phase were related to IL-6. In conclusion, our study demonstrate d that rhIL-6 can be administered safely to patients with refractory M M, but the cell cycle recruitment approach was not sufficiently effect ive to be of clinical value. (C) 1998 Published by Elsevier Science Lt d. All rights reserved.