1. Follicular lymphoma Every patient should be treated at diagnosis
Michele Ghielmini
Medical Oncology Dept
Oncology Institute of Southern Switzerland
Bellinzona

2. W + W vs. immediate chemotherapy: only old and underpowered studies
W+W vs. ProMACE-MOPP
89 pts
Young, 1988
W+W vs. Prednimustine
130 pts
Brice, 1997
W+W vs. Chlorambucil
309 pts
Ardeshna, 2003
Overall survival
With permission from The Lancet, Ardeshna K M et al., The Lancet, August 2003, Vol ):

3. What is the point of delayng treatment of 3 years?
W+W lasts a median of 3 years
What is the point of delayng treatment of 3 years?

4. New treatments have improved survival
1002 FL patients
3 decades
Barcelona
London
Bellinzona
Novara
Conconi et al. 2015; in press

5. Meta-analysis of chemo vs. R-chemo: overall survival
Schulz H, et al. J Natl Cancer Inst 2007; 99:706–714.

6. Risk of follicular lymphoma transformation by initial therapy
Link B K et al. J Clin Oncol 2013;31:

7. FL: STIL vs. BRIGHT study (PFS)12 24 36 48 60 72 84 96
Time (months)
Rummel MJ, et al. Lancet
Flinn IW et al. ASH 2012; abstract 902. 2 2

8. BRIGHT-Phase III Study R-Benda vs. R-CHOP/R-CVP
Quality of life
In all pts, GHS/QOL score significantly improved from baseline to final visit with BR vs R-CHOP/R-CVP
GHS/QOL
iNHL pts:
BR: +2.1
R-CHOP/R-CVP: -6.3 (p=0.0021)
MCL pts:
BR: +10.9
R-CHOP/R-CVP: +1.6 (p=0.0654)
Mean (SEM) changefrom baseline in QLQ-C30 functioning scales
Adapted from Burke JM et al. ASH 2012; abstract 155.

9. UK intergroup trial (n=600) Asymptomatic non-bulky FL
N D O M I S A T I O N
ARM A
Watch and Wait
R R R R R R R R R R R R
Rx4
months
Clinic visits
Continued
follow up
ARM B
Rituximab Induction
ARM C
Rituximab Induction
& maintenance

10. UK study on W+W patients: Time to Initiation of New Therapy (TINT)
Proportion of patients with no new
treatment initiated
W+W R4
R4 + M
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0 1 2 3 4 5
Years from randomisation
ICML update: R + M reduces anxiety compared to W+W
Ardeshna et al., Abstr. 19, ICML-11, 2011

11. Risk of Transformation
Ardeshna et al, Lancet Oncol 15:424, 2014

12. Rituximab maintenance for how long? SAKK 35/03 study design
SAKK 35/03 trial
Short maintenance Rituximab 375 mg/m² q2 months x 4
Randomization
PR + CR
Rituximab 375 mg/m²
qwk x 4
restage week 12
SD + PD off study
Rituximab 375 mg/m² q2 months until progression (max. 5 years)
Long maintenance
Taverna CJ, et al. ASH 2013 12

13. SAKK 35/03: 1 vs. 5 years maintenance
EFS
PFS
Long-term maintenance
Median 5.3 y
Short-term maintenance
Median 3.4 y
P=0.14
Long-term maintenance
Median 7.4 y
Short-term maintenance
Median 3.5 y
P=0.04
Taverna C. et al. ASH 2013

14. Conclusion: is R2 as active as R-chemo?
R2 in first line FL
MDACC
CALGB n= 50 66
Lenalidomide
20 mg d1-21 x 6
20 g d1-21 x 12
Rituximab
375 mg/m2 qd 4 wks x 6
375 mg/m2 weekly x 4
+ cycle 4, 6, 8, 10
Median age 58 53
FLIPI ≥ 2
78%
69% RR
98%
93% CR
87%
72%
2y. PFS
89% -
Ref
Fowler et al.
Abstr. 901, ASH 2012
Martin et al.
Abstr. 63, ICML-12, 2013
Conclusion: is R2 as active as R-chemo?

15. Radio-Immunotherapy as Initial Therapy for Indolent NHL
I-131 Tositumomab
n = 76 patients, 97% RR, 76% CR
90-Y Ibritumomab
n = 50 patients, 94% RR, 86% CR
Kaminski MS, et al. N Engl J Med. 2005;352(5):
Ibatici A, et al. Br J Haematol. 2014;164(5):

16. Which one do you consider to be the loser?
I am in remission since 7 years!
I have cancer and they don’t want to treat me!

17. Conclusions Patients are happier when they are free of disease
Treatment of FL is today well tolerated and achieves long PFS
Patient-friendly options are single agent, long term rituximab, R2 or R-bendamustine
Treatment reduces the risk of transformation