1. Morie Gertz Chair Dept. of Medicine
Treatment Strategies in Amyloidosis
Scottsdale, Arizona
Rochester, Minnesota
Jacksonville, Florida

2. Amyloidosis 2010 New Diagnostic Strategies New methods of monitoring
New prognostic indicators
New therapies

3. Mel Dex for Non SCT candidates AL; Long Term F/U
Palladini, G. et al. Blood 2007;110:
Copyright ©2007 American Society of Hematology. Copyright restrictions may apply.

4. Mel Dex for Non SCT candidates AL
40 consecutive non SCT pts Worse outcomes related to Hi cardiac #’s
10.5 mo
BJH 143:369-73

5. Intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with AL and severe cardiac involvement
Median OS 17.5 mos; 28% mortality first 3 months
Blood Apr 7. [Epub ahead of print]

6. Kastritis 428 CRd AL Dex 20 d1-4 CTX 100mg/d x10
R dose escalation MTD 15
N=26 17 untreated 5/9 treated prior BTZ
@dose max 9/13 responses 69%
All pts 14/23 61% RR
5/23 organ responses; PFS 10 mos
For renal failure Cr > 2.5 CTX 50 R 15qod
RR 3/8

7. MDR for AL MDR AL Ph 1 dose escalation R 5→20 d1-21
M .17 mg/kg/d 1-4; D40 1-4q28
LMWH for DVT proph
26 evaluable , R 15 6 deaths
CR 42%; PR 9/26 ORR 58% organ response 50% EFS OS
Moreau Blood 2010 in press

8. Mayo Clinic survival post SCT
Median 94 mos.

9. SCT outcomes by stage N=443

10. Survival: Landmark analysis Cardiac Amyloidosis SCT
Considering only patients surviving beyond day 100
Median OS 76 mos (95% CI; 69, NR)
Follow up from SCT (mos)

11. Day 100 all cause mortality before & after 2006
7.0%
P=0.09
12.1%

12. Mutivariable Survival Analysis
Only Troponin p=.02 & BNP p=.008 predictive of survival

13. Bortezomib is active in AL
Blood Jun 4. [Epub ahead of print]

14. Bortezomib +/-Dex
Untreated patients had a 47% CR rate. Twice weekly bortezomib (P = .041) higher response rates.
Cardiac response 29%
Hematologic responses were associated with a cardiac response and NT-proBNP reduction.
The 1-year survival is 76%.
NT-proBNP was independently associated with survival (P = .001)
J Clin Oncol Feb 20;28(6):

15. C neither 3-month landmark
Survival of patients according to (A) hematologic and (B) proBNP response
By FLC
BNP dec 30%
A heme & BNP
B 1 only
C neither 3-month landmark
Kastritis, E. et al. J Clin Oncol; 28:

16. Wechalekar, A. D. et al. Blood 2007;109:457-464
CTD Therapy of AL
Wechalekar, A. D. et al. Blood 2007;109:
Copyright ©2007 American Society of Hematology. Copyright restrictions may apply.

17. Dispenzieri, A. et al. Blood 2007;109:465-470
REV DEX for AL
Dispenzieri, A. et al. Blood 2007;109:
Copyright ©2007 American Society of Hematology. Copyright restrictions may apply.

18. Dispenzieri, A. et al. Blood 2007;109:465-470
REV DEX RESPONSES
Dispenzieri, A. et al. Blood 2007;109:
Copyright ©2007 American Society of Hematology. Copyright restrictions may apply.

19. MD vs MDB in Newly Diagnosed Immunoglobulin Light Chain Amyloidosis (AL) Patients Who Are Not Candidates for ASCT MD
M=0.22 mg/kg/d, days courses at 6-week intervals 95
Untreated AL patients; ineligible for ASCT (N = 190*)
Primary endpoint: PFS at 2 years
60%80%
Stratify as cardiac stage I or II
MDB Arm MD + Bortezomib 1.3 mg/m2
days 1,4,8,11 95
*Eighty-six required for each arm for a=0.05 (two-sided) and b= Additional 18 patients allowed for drops-outs and ineligibles

20. Conclusions
For patients who can be transplanted safely SCT remains a preferred option
For non transplant candidates Mel Dex remains the default standard
Bortezomib has clear activity but its integration into practice is not fully defined
Imid therapy including CTD & MDR is being explored

21. Treatment of AL
Transplant Eligibility Criteria
“Physiologic” Age ≤ 70 years
Performance Score ≤ 2
TnT < 0.06 ng/ml
CrCl ≥ 30 ml/min *
(unless on chronic dialysis)
NYHA Class I/II*
No more than 2 organs significantly involved
*Selected patients may become eligible for PBSCT with cardiac and renal transplantation
v1 Jan 2010 21

22. Treatment of AL Amyloidosis– off-study
Newly Diagnosed AL Amyloidosis
Transplant Eligible
Transplant Ineligible
SCT with Mel
Mel-Dex
Consider second-line therapy if:
heme PR not achieved at day +100
organ progression at 6 months
Treat to max response + 2
(no more than 10 cycles)
Consider second-line therapy if:
heme MR not seen after 4 cycles
organ progression at 6 months
Msmart.org
v1 Jan 2010 22

23. Relapsed AL Amyloidosis
Treatment of AL Amyloidosis– off-study
Relapsed AL Amyloidosis
Mel-Dex, Len-Dex,
Bortezomib or Dex
v1 Jan 2010

24. Low dose regimen or clin trial
Cardiac only
OHT then HDM/ASCT
Cardiac stage III
Multiorgan
Low dose regimen or clin trial CR
Obs
HDM/
ASCT PR
Obs or Novel Agent
YES NR
EARLY DIAGNOSIS, ACCURATE TYPING
Eligible for ASCT ?
Novel Agent
Cardiac staging CR
Obs NO
MDex, Clin trial
Non-CR
Novel Agent 24

25. Solid Organ Transplantation
Renal Transplantation and Stem Cell Transplantation
Which should come first?
Who is eligible?

28. Cardiac Transplantation