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 myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated 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 chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment 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 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two patients an increase (mean 7.7%) in LI of mononuclear bone marrow cells during the rhIL-6 treatment was demonstrated and in one patient a decrease of 2.8% was seen. Assessment of PCLI demonstrated an increase 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 patients developed mild constitutional adverse events (AE) well known in patients treated with IL-6, and none of the AE in the subsequent chemotherapy phase were related to IL-6. In conclusion, our study demonstrated that rhIL-6 can be administered safely to patients with refractory MM, but the cell cycle recruitment approach was not sufficiently effective to be of clinical value.
Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
P
P
de Nully Brown
P O
PO
Jensen
M
M
Diamant
B T
BT
Mortensen
D
D
Hovgaard
P
P
Gimsing
N I
NI
Nissen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002452:Cell Count; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D010950:Plasma Cells / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012074:Remission Induction; D016196:S Phase
D000970:Antineoplastic Agents; D015850:Interleukin-6; D011994:Recombinant Proteins