S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

• Published in: Leukemia research 1998-11, Vol.22 (11), p.983-989
• Main Authors: de Nully Brown, Peter, Østrup Jensen, Peter, Diamant, Marcus, Mortensen, Børge T, Hovgaard, Doris, Gimsing, Peter, Nissen, Nis I
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Cell Count; Female; Humans; Immunotherapy; Injections, Subcutaneous; Interleukin-6 - administration & dosage; Interleukin-6 - pharmacology; Interleukin-6 - toxicity; Male; Medical sciences; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Multiple Myeloma - therapy; Pharmacology. Drug treatments; Plasma Cells - drug effects; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Remission Induction; S Phase
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(98)00098-8

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 μg/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.