1. Controversies in Transplant for Lymphoma
Andy Chen, MD PhD
Center for Hematologic Malignancies
Oregon Health & Science University
September 2013

2. Disclosures Clinical trials - Genentech, Otsuka, Seattle Genetics
Advisory boards - Genentech, Seattle Genetics

3. NMDP Guidelines for Hodgkins
AutoSCT indicated for:
No initial CR
First or subsequent relapse
NCCN guidelines:
AutoSCT for relapsed/refractory Hodgkins not amenable to radiation therapy

4. Hodgkins: AutoSCT vs conventional chemo
GHSG randomized trial
3 yr FFTF 55 vs 34%
No difference in OS
Similar results in BNLI study
Schmitz, Lancet, 2002

5. Hodgkins: pre-SCT disease status
PFS
French series
N=111
MSKCC series
N=153
Moskowitz, Blood, 2010
Devillier, Haematologica, 2012

6. Hodgkins: PET negativity & AutoSCT
MSKCC study
- GVD salvage if PET+ after ICE
Should PET negativity be the goal before AutoSCT?
Moskowitz, Blood, 2012

7. Hodgkins: Brentuximab & autoSCT
Brentuximab (SGN-35): antibody drug conjugate against CD30
Approved for relapse after auto or failure of 2 chemo regimens
Response rate >70% including >30% CR
- Use as 2nd salvage to achieve PETneg before SCT?
- Use as 1st salvage – with or without chemo?
- Maintenance after autoSCT?

8. ASBMT Key Guidelines for DLBCL
AutoSCT recommended for chemosensitive relapse
AutoSCT not recommended as first line therapy
Age is not contraindication for autoSCT
Auto vs Allo SCT: competing risks & selection bias
NCCN guidelines similar
Oliansky, BBMT, 2011

9. DLBCL: Conventional Tx vs BMT
EFS OS
‘PARMA’ study: N 215, median f/u 5 yrs
- randomized chemosensitive patients
Prior to Rituximab era
Philip, NEJM, 1995

10. CORAL DHAP vs ICE maintenance Rituximab
modern efficacy of salvage+Auto
Gisselbrecht, JCO, 2010

11. DLBCL: R-DHAP vs R-ICE (CORAL)
No difference overall between R-ICE and R-DHAP
Gisselbrecht, JCO, 2010

12. DLBCL subtype: DHAP vs ICE
cell of origin by Hans IHC
R-DHAP
R-ICE
PFS
PFS
R-DHAP may be superior for germinal center type DLBCL
Thieblemont, JCO, 2011

13. DLBCL: Relapse ≤ 1 yr
60% of early relapse do not respond to 1st salvage
- If respond & proceed to autoSCT, then 3 yr EFS = 39%
Gisselbrecht, JCO, 2010

14. Myc+ and AutoSCT CORAL sub-analysis: - N = 28 (16% original study)
From start of salvage
CORAL sub-analysis:
- N = 28 (16% original study)
- Myc single vs double hit same
- R-DHAP & R-ICE same
- GCB vs ABC same if Myc+
Cuccuini, Blood, 2012

15. AutoSCT and Radioimmunotherapy
RIT: antibody conjugated to radiation
Beta emitter: Yttrium-90 Ibritumomab tiuxetan (Zevalin)
Gamma emitter: Iodine-131 Tositumomab (Bexxar)
Does RIT improve efficacy of high dose conditioning regimen?
BMT CTN 0401: R-BEAM vs BEXXAR-BEAM

16. DLBCL: BEXXAR-BEAM (CTN 0401)
No difference in PFS or OS
Significant increase in mucositis with BEXXAR
Vose, JCO, 2013

17. AutoSCT in 1st Response for DLBCL
Multiple (>10) randomized studies in pre-Rituximab era
Two meta-analyses: No benefit in EFS or OS
Controversial whether benefit in high risk IPI
Not recommended in ASBMT policy guidelines
What is role of AutoSCT in PR/CR1 after R-CHOP for DLBCL?

18. DLBCL: Consolidative AutoSCT
SWOG 9704
Italian DLCL04
Criteria
IPI 3-5
aaIPI 2-3
Chemo
(R)-CHOP x8
R-CHOP-14 x8
BMT
CBV, BEAM or TBI
R-MAD + BEAM N
370
392
PFS
2 yr: 69 vs 56 %
2 yr: 71 vs 59 % OS
2 yr: 74 vs 71 %
2 yr: 83 vs 83 %
Stiff, ASCO, 2011
Vitolo, ICML, 2011

19. ASBMT Guidelines for Follicular lymphoma
AutoSCT improves PFS and OS as salvage therapy based on pre-Rituximab data
AutoSCT recommended for transformed Follicular based on expert opinion and accepted practice
Not recommend as first line therapy/consolidation
Auto vs Allo: competing risks & selection bias
Reduced intensity conditioning acceptable for Allo
Oliansky, BBMT, 2010

20. Follicular: AutoSCT vs conventional chemo
PFS
‘CUP’ trial – improves PFS & OS
- no benefit from purging
- prior to Rituximab era
Schmitz, Lancet, 2002

21. Follicular: AutoSCT vs conventional chemo
EFS OS
p=0.05
p=0.05
Impact of AutoSCT at 1st relapse on Pts in FL2000 study
Frontline R-CHVP, N=70
Caveat: AutoSCT not randomized
Le Gouill, Haematologica, 2011

22. Follicular: Timing of AutoSCT
Nebraska series
DFCI/St Bart series
Vose, BBMT, 2008
Rohatiner, JCO, 2007

23. Follicular: Maintenance Rituximab post-SCT
EBMT randomized study: relapsed chemosensitive FL
Caveat: No prior rituximab
Pettengell, JCO, 2013

24. Follicular Auto vs Allo
Adjusted OS
CIBMTR series
Similar results in EBMT series
van Besien, Blood, 2003

25. Follicular Allo: Ablative vs Reduced intensity
PFS OS
CIBMTR series: HLA matched siblings
Hari, BBMT, 2008

26. Transformed Follicular: R-chemo vs Auto vs Allo
PFS OS
Canadian retrospective series: N 172, median f/u 7 yrs
Villa, JCO, 2013

27. NMDP Guideline for Mantle Cell
Following initial therapy
Not specify Auto vs Allo
Not discuss relapse/refractory
NCCN guidelines:
Auto in CR1
Allo in CR2

28. Mantle: Upfront AutoSCT
PFS OS
MCLnetwork randomized study
- CHOP induction (No Rtx)
Dreyling, Blood, 2005

29. Mantle: Induction chemo pre-SCT
PFS
MCLnet ‘Younger’ trial
improved MRD
trend for OS
updated 4 yr f/u
median PFS 88 vs 46 mos
Hermine, ASH, 2010 & 2012

30. Mantle: MRD status
AutoSCT effect on MRD rate in DHAP arm: 73% -> 83%
Similar impact of MRDneg in R-CHOP + Rtx maint (no SCT)
Pott, ASH, 2010 & Blood, 2010

31. Mantle: Allogeneic SCT
European multicenter
- N 70, median f/u 24 mos
relapsed/refractory
67% prior auto
reduced intensity
Le Gouill, Ann Onc, 2012

32. AlloSCT after Auto failure in NHL
Prognostic factors:
early failure of auto
disease status
performance status
CIBMTR series
N 263
median f/u 68 mos
Freytes, BBMT, 2012

33. Future directions: NHL & SCT
Identification of high risk patients
Alternative chemo and/or Allo
Novel therapies
Better disease control before SCT
Maintenance after SCT
Critical need in DLBCL, especially Myc+/double hit
Next gen Antibodies & Antibody drug conjugates
Signaling inhibitors (BTK, Syk, PI3K)