S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma
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S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma. / de Nully Brown, P; Jensen, P O; Diamant, M; Mortensen, B T; Hovgaard, D; Gimsing, P; Nissen, N I.
In: Leukemia Research, Vol. 22, No. 11, 11.1998, p. 983-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma
AU - de Nully Brown, P
AU - Jensen, P O
AU - Diamant, M
AU - Mortensen, B T
AU - Hovgaard, D
AU - Gimsing, P
AU - Nissen, N I
PY - 1998/11
Y1 - 1998/11
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Antineoplastic Agents
KW - Cell Count
KW - Female
KW - Humans
KW - Injections, Subcutaneous
KW - Interleukin-6
KW - Male
KW - Middle Aged
KW - Multiple Myeloma
KW - Plasma Cells
KW - Recombinant Proteins
KW - Remission Induction
KW - S Phase
KW - Clinical Trial
KW - Clinical Trial, Phase I
KW - Clinical Trial, Phase II
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - Journal article
C2 - 9783799
VL - 22
SP - 983
EP - 989
JO - Leukemia Research
JF - Leukemia Research
SN - 0145-2126
IS - 11
ER -
ID: 181873866