1. R-CHOP Stem Cell Transplantation for Follicular Lymphoma
John P. Leonard, M.D.
Richard T. Silver Distinguished Professor of Hematology and Medical Oncology
Associate Dean for Clinical Research
Vice Chairman, Department of Medicine

2. Disclosures Consulting advice:
Seattle Genetics, Genentech, Pharmacyclics, Biotest, Celgene, Medimmune, Gilead

3. What do we expect going forward?
Case
43 year-old male, follicular, grade NHL, high risk FLIPI receives 6 cycles of chemoimmunotherapy
Does not achieve a CR
What do we expect going forward?
What do we do?

4. Overall survival high-risk FLIPI
5 year OS
52%
10 year OS
35%
Solal-Celigny et al,
Blood 2004

5. PET negative (CR) vs PET positive (no CR) after induction therapy for FL - PFS
PRIMA
Observation
Group
Maintenance
Trotman et al
JCO 2011

6. PET negative (CR) vs PET positive (no CR) after induction therapy for FL - OS
Combined
observation and
Maintenance
groups
45% of PET + are high risk FLIPI
Trotman et al
JCO 2011

7. Issues to consider in this patient’s status (no CR after chemoimmunotherapy)
Median PFS with observation is probably about 2 years
Median PFS with maintenance rituximab is difficult to define but 40% progress in 2-3 year range
Lack of CR correlates with worsened overall survival

8. Radioimmunotherapy impact on PET positive (no CR) status after induction therapy for FL – PFS after Y-90 RIT
Median 2 year
PFS in PR
Treated w/ RIT
FIT study
Morschhauser et al
JCO 2013

9. PFS and OS after R-CHOP or CHOP-I-131 tositumomab by FLIPI
Note:
Includes both
CR and PR
pts
S0016
Press et al
Clin Can Res 2013

10. Issues to consider in this patient’s status (no CR after chemoimmunotherapy)
RIT appears to associate with some durable remissions in this population but most patients relapse in 2+ year time frame
No clear benefit of RIT vs maintenance R but possible
OS status unclear after RIT in this specific population (our case)
High risk FLIPI + PET positive/no CR after induction may be an adverse “double whammy” that maintenance R and RIT modestly impact

11. What other options will be out there for this patient when he has his expected relapse?
Chemoimmunotherapy (B-R, R-CHOP)
Lenalidomide
Novel anti-CD20s
Anti-apoptotic agents
PI3K inhibitors
BTK inhibitors

12. Regarding the other options….. Regarding the other options….
What fraction of patients, if any, can have durable remissions with these agents?
If comparable, how does QOL (short-term vs chronic) compare?
SCT data limited in modern era with respect to use in first PR (must extrapolate from relapsed setting)

13. CUP trial in of AuSCT in relapsed FL
Schouten, et al, JCO 2003, 21(21):

14. CUP trial - PFS
Schouten, et al, JCO 2003, 21(21):

15. CUP trial - OS
Schouten, et al, JCO 2003, 21(21):

16. Remission Duration of Patients Receiving AuSCT for FL in Second or Later Remission
St. Barts and DFCI
Rohatiner et al. J Clin Oncol. 2007;25:

17. 280 enrolled and randomized (purged/non-purged)
Rituximab purging and/or maintenance in R-naive patients with chemosensitive relapsed FL.
280 enrolled and randomized (purged/non-purged)
Approximately 200 transplanted (100 purged/100 non purged)
Approximately 50 maintenance R in each arm
Rituximab naïve, 80% 2 prior regimens, 30% CR, 70% VGPR
Pettengell R et al. JCO 2013;31:

18. Progression-free survival by treatment arm
Pettengell R et al. JCO 2013;31:

19. AuSCT at first relapse after R-CHVP-IFN
PFS and OS
After ASCT vs no ASCT
175 relapsers after FL2000 study
(R-CHVP-I vs CHVP-I)
70 relapsers after R-CHVP-I
Various second line rx (65%
included R)
13 with ASCT
ASCT associated with improved
PFS and OS
Le Gouill S, et al, Haematologica 2011

20. Allo vs. Auto SCT IBMTR Registry data OS DFS N = 904 patients with FL
Transplants between
Probability of improved long-term OS not improved by allo ASCT
Significant heterogeneity in subjects
DFS OS
van Besien K, et al, Blood 102:2003;

21. Allo vs. non-myeloablative SCT in FL
Retrospective, 88 pts (48 allo, 40 miniallo)
Characteristics
Miniallo pts were older and more often had prior autoSCT
Outcomes
Relapse rate 13% (allo) vs 28% (miniallo)
1 year TRM 33% (allo) vs 28% (miniallo)
2 year OS and PFS (allo) 52% and 46%
2 year OS and PFS (miniallo) 53% and 40%
Chemosensitive disease and no prior AutoSCT correlated with outcome
Rodriguez R, et al, Biol Blood Marrow Transplant, 2006;12(12):

22. Conclusions
High risk FLIPI at diagnosis and lack of CR with front line therapy correlate with less favorable PFS and OS
Still, maintenance R and RIT can associate with good outcomes in a subset of patients
Novel agents warrant study in this setting
AuSCT is associated with high PFS and OS rates in this group in non-comparative trials and should be strongly considered