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.
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 microg/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.
Rossi
J-F
JF
Service d'Hématologie et d'Oncologie Médicale, CHU Montpellier, avenue du Doyen Giraud, Montpellier Cédex, France. jf-rossi@chu-montpellier.fr
Fegueux
N
N
Lu
Z Y
ZY
Legouffe
E
E
Exbrayat
C
C
Bozonnat
M-C
MC
Navarro
R
R
Lopez
E
E
Quittet
P
P
Daures
J-P
JP
Rouillé
V
V
Kanouni
T
T
Widjenes
J
J
Klein
B
B
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology / Q000401:mortality; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D010865:Pilot Projects; D033581:Stem Cell Transplantation / Q000379:methods; D014182:Transplantation, Autologous
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019653:Myeloablative Agonists; D003907:Dexamethasone; D002097:C-Reactive Protein; D008558:Melphalan