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Conditioning Regimens

Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects

Bone Marrow Transplantation volume 36, pages 771–779 (2005)Cite this article

Summary:

Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m2) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m2. Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 μg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM.

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Authors and Affiliations

  1. Service d'Hématologie et d'Oncologie Médicale, CHU Montpellier, avenue du Doyen Giraud, Montpellier Cédex, France

    J-F Rossi, N Fegueux, E Legouffe, C Exbrayat, R Navarro, E Lopez, P Quittet, V Rouillé & T Kanouni

  2. Unité de Thérapie Cellulaire et Génique, Hôpital Saint-Eloi, CHU Montpellier, Avenue Augustin Fliche, Montpellier Cédex, France

    Z Y Lu & B Klein

  3. Unité de Biostatistique, d'épidémiologie et de recherche clinique, avenue du Doyen Giraud, Montpellier Cédex, France

    M-C Bozonnat & J-P Daures

  4. Diaclone Research, boulevard Alexandre Flemming, Besançon Cédex, France

    J Widjenes

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Correspondence to J-F Rossi.

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Rossi, JF., Fegueux, N., Lu, Z. et al. Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects. Bone Marrow Transplant 36, 771–779 (2005). https://doi.org/10.1038/sj.bmt.1705138

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