Radiotherapy is unnecessary in elderly
patients with localized aggressive non
Hodgkin Lymphoma : results of the
LNH 93-4 study
G. Fillet, C. Bonnet,N. Mounier, C. Thieblemont,
C. Fermé, B. Quesnel, C. Martin, M. Blanc,
Th. Conroy, A.M. Penny, T. Petrella, F. Reyes
for the GELA, CHU - Sart Tilman, Liège, Belgium
GELA - LNH 93
Third multicenter study on aggressive lymphoma
Number of age adjusted IPI factors
0 1 2 3
70 yrs LNH93-6/7
GELA
LOCALIZED AGGRESSIVE
LYMPHOMA
BACKGROUND. Brief chemotherapy followed
by IFRT is considered as the standard treatment.
• 3 cycles of CHOP + IFRT > 8 cycles of CHOP
(Miller et al., NEJM, 1998, 339:21)
However patients enrolled in this study were
heterogeneous with regard to major prognostic factors
of the IPI.
PURPOSE. The GELA designed the present
LNH 93-4 study to compare radiotherapy versus
nothing after 4 cycles of chemotherapy.
LNH 93-4
inclusion criteria
• Age 60 y
Stage : I - II
• a.a. IPI = 0 LDH : 1 N
PS : 2 : 10
• Cut-off date : August 1, 2001
40
LNH 93-4
35
Median age : 68 yrs.
30
Patients > 70 yrs : 46%.
25
20
15
10
5
0
60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85
Age
LNH 93-4
CHOP CHOP + IFRT
Gender (male) 52 % 51 % NS
G + H+ M 86 % 83 % NS
T-cell 9% 7% NS
Stage I 69 % 67 % NS
ECOG 0 73 % 72 % NS
E.N. sites 1 60 % 54 % NS
mass 10 cm 9% 9% NS
LNH 93-4
RESPONSE TO TREATMENT
CHOP CHOP + IFRT
(%) (%)
CR 92 89
PR + Failure 5 8
Death 3 3
(NS)
LNH 93-4
Event Free Survival
100
%SURVIVAL
75
N=224
50
CHOP N=244
CHOP+IFRT
25
m f-up 55 mo. p=0.36
0
0 1 2 3 4 5 6 7 8 9
YEARS.
LNH 93-4
Overall survival
100
N=224
%SURVIVAL
75
50 N=244
CHOP
25
CHOP+IFRT
p=0.14
0
0 1 2 3 4 5 6 7 8 9
YEARS.
LNH 93-4
CHOP CHOP + IFRT p
5 yrs EFS 67 % 62 % 0.45
5 yrs OS 78 % 68 % 0.14
LNH 93-4
Factors P RR 95% CI
Cox analysis for event free survival
Stage II <0.0001 2.0 (1.5-2.8)
Male sex 0.054 1.4 (1.0-1.9)
Cox analysis for overall survival
Stage II 0.0003 1.9 (1.3-2.8)
Male sex 0.018 1.6 (1.1-2.2)
LNH 93-4
RELAPSES
CHOP CHOP + IFRT
(n = 55) (n = 66)
locoregional (%) 45 23
distant (%) 55 76
median delay from
diagnosis (mo) 11 15
LNH 93-4
DEATHS
CHOP CHOP + IFRT
(n = 53) (n = 72)
during induction 6 8
lymphoma 37 48
other malignancies 5 7
(5 within irradiation field)
other causes 4 4
unknown 1 5
468
Eligible
254 214
< 70 yrs 70 yrs
In each subset clinical characteristics
well balanced between the two arms
LNH 93-4
Patients 70 years and older
Event Free Survival
100
%SURVIVAL
75
N=108
50
CHOP
CHOP+IFRT N=106
25
p=0.04
0
0 1 2 3 4 5 6 7 8 9
YEARS.
LNH 93-4
Patients 70 years old and older
Overall Survival
100
%SURVIVAL
75 N=108
50
N=106
CHOP
CHOP+IFRT
25
p=0.03
0
0 1 2 3 4 5 6 7 8 9
YEARS.
PATIENTS 70 yrs
DEATHS
CHOP CHOP + IFRT P
(n = 21) (n = 35) 0.02
during induction 4 5 NS
lymphoma 13 22 NS
other malignancies 1 5 NS
(3 within irradiation field)
other causes 2 2
unknown 1 1
CONCLUSIONS : LNH 93-4
• First prospective randomized study comparing
chemotherapy alone with the same chemotherapy
followed by IFRT.
• After 4 cycles of CHOP, IFRT does not increase CR,
EFS or OS in elderly patients with localized
aggressive NHL.
• After 69 yrs of age, IFRT following chemotherapy
has a negative impact on survival.
CONCLUSIONS : LNH 93-4
• A 5 yrs EFS of 67 % after chemotherapy is
unsatisfactory.
• Current recommendation of the GELA :
6 - 8 cycles of CHOP21 + Rituximab d1