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S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma
P de Nully Brown1, P O Jensen, M Diamant
1Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
Abstract:
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.
Insights
Recombinant human interleukin-6 (rhIL-6) was administered to refractory multiple myeloma (MM) patients to increase chemotherapy sensitivity. This approach was safe but did not significantly improve the plasma cell labeling index or lead to remission.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Multiple myeloma (MM) exhibits a low plasma cell labeling index (PCLI), correlating with poor remission rates post-chemotherapy.
- Interleukin-6 (IL-6) is a key growth factor for myeloma cells.
- Enhancing myeloma cell S-phase proportion may increase chemosensitivity.
Purpose of the Study:
- To evaluate the efficacy of recombinant human IL-6 (rhIL-6) in increasing the S-phase proportion of myeloma cells.
- To assess if rhIL-6 pretreatment followed by chemotherapy improves remission rates in refractory MM patients.
Main Methods:
- Fifteen refractory MM patients received rhIL-6 (2.5, 5.0, or 10.0 microg/kg daily for 5 days) followed by chemotherapy.
- Plasma cell labeling index (PCLI) and mononuclear bone marrow cell labeling index (LI) were monitored.
- Treatment cycles and adverse events were recorded.
Main Results:
- rhIL-6 administration was safe, with mild constitutional adverse events observed in 14/15 patients.
- No statistically significant overall change in labeling index was observed.
- One patient showed a PCLI increase of 2.9%, another a decrease of 1.9%.
- None of the 15 patients achieved remission.
Conclusions:
- rhIL-6 can be safely administered to refractory MM patients.
- The cell cycle recruitment strategy using rhIL-6 did not demonstrate sufficient clinical effectiveness for remission induction.