Predictors of clinical response to interleukin-2--based immunotherapy in melanoma patients: a French multiinstitutional study.
OBJECTIVE
Various parameters have been reported to be correlated with response to interleukin-2 (IL-2) therapy. A multiinstitutional study was performed to assess by multivariate analysis the predictive value of known clinical and biologic melanoma prognostic markers recorded before the onset of IL-2 therapy on the likelihood of objective clinical response.


METHODS
Serum C-reactive protein (CRP), IL-6, and lactate dehydrogenase (LDH) levels were measured in 81 metastatic melanoma patients included in different IL-2-based regimens before the starting of IL-2-therapy. Clinically defined prognostic groups, i.e., patients with superficial or visceral metastases, were also analyzed for response correlates. Patients were evaluated for response to treatment 4 to 6 weeks after completion of one course of therapy.


RESULTS
On univariate analysis, the pretreatment values of CRP (P = .001), IL-6 (P = .007), and LDH (P = .02) and site of metastases (P = .0004) were correlated with clinical response. However, only CRP (P < .007) and clinically defined group (P < .004) were independent predictors on multifactorial analysis. Indeed, when adjusted to CRP, IL-6 tended to improve patient selection, but did not reach statistical significance (P = .07). Furthermore, using multivariate survival analysis based on the Cox proportional hazards model, only CRP was found to be an independent prognostic factor for survival (P < .0001).


CONCLUSIONS
In this study, patients with high serum levels of CRP and/or visceral organ involvement before therapy were unlikely to respond to IL-2 therapy. Therefore, clinical classification based on the site of metastases and serum CRP determination before the start of IL-2 therapy may help to improve selection of melanoma patients who may benefit from IL-2 and could prevent unnecessary morbidity.
Tartour
E
E
French Cancer Centers' Immunotherapy Group, Paris, France.
Blay
J Y
JY
Dorval
T
T
Escudier
B
B
Mosseri
V
V
Douillard
J Y
JY
Deneux
L
L
Gorin
I
I
Negrier
S
S
Mathiot
C
C
Pouillart
P
P
Fridman
W H
WH
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000302:isolation & purification; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005602:France; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016019:Survival Analysis
D007376:Interleukin-2; D015850:Interleukin-6; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase; D002945:Cisplatin