Optimal Use of Transplant for Myeloma

Early-Late-nonablative

Koen van Besien, MD, PhDWeill Cornell Medical College

Optimal Use of Transplant for Myeloma

Transplant Early!

Consider Allogeneic Transplant!

Koen van Besien, MD, PhDWeill Cornell Medical College

Why Transplant Early?

• It is the standard• It is less toxic than alternatives• It is curative therapy

High-Dose Therapy and Autologous SCT Improves PFS and OS in Younger Patients

Child JA, et al. N Engl J Med. 2003;348:1875-1883.; Attal M, et al. N Engl J Med. 1996;335:91-97.

ASCT vs. Conventional CTResults of Randomized Studies

Attal, et al. 1996 IFM90CT

Auto Tx

Fermand, et al. 2005 MAG91CT

Auto Tx

Child, et al. 2003 MRC7CT

Auto Tx

Palumbo, et al. 2004 IMMSGCT

Auto Tx

Blade, et al. 2005 PETHEMACT

Auto Tx

Barlogie, Kyle, et al. 2006 USIGCT

Auto Tx

100

100

96

94

200

201

98

97

83

81

255

261

5

22

18

27

20

36

19

25a

9

44

20

32

6

25

16

28

11

30

33

42

11

11

16%at 7

years17%

44

57

48

48

42.3

54.1

43

58+

66

61

38%at 7

years38%

.03

.03

< .001

Patients(n)

OS(months) P Value

EFS(months)

CR(%)

CT = chemotherapy; Auto Tx = autologous therapy; IFM = Intergroupe Francais du Myelome; IMMSG = Italian Multiple Myeloma Study Group; MAG = Group Myelome Autographe; MRC = Medical Research Council; USIG = US Intergroup

aP = .07

Why Transplant Early?

• It is the standard.• It is less toxic than alternatives• It is curative therapy

0

10

20

30

40

50

60

70

Estimated medianOS

Median EFS TWiSTT*

PSCT (early)

PSCT (late)

Mon

ths

HDT/PSCT: Upfront vs. Rescue Treatment Show Similar OS but Better QOL with Early SCT

*Time without symptoms and treatment toxicity Fermand J, et al. Blood. 1998;92:3131-3136

64.6 64.0

39.0

13.0

27.822.3

P = .92

n=202

14

Impact of ASCT on QOL of FL patients

Andresen et alLeuk & Lymph, 2012; 53: 386

Why Transplant Early?

• It is the standard• It induces more remissions• It is curative therapy

Martinez-Lopez et al Blood. 2011;118(3):529-534

CR vs. nCR/VGPR/PR vs. Menos

Martinez-Lopez et al Blood. 2011;118(3):529-534

Abstract

Why Transplant Early?

• It is the standard• It is less toxic than alternatives• Delaying curative therapy until after disease

recurrence may result in loss of curability

• Refractory Myeloma

• Transient antitumor effect CTX, then TBI, thiotepa with T-cell depleted allograft

• Progressive disease was documented before day 70

• 2nd DLI resulted in complete disappearance of any disease

• GVHD developed revealing a GVM effect

Tricot G. Blood 87;3 1996 1196-1198.

Allo Tx

• Graft vs. Myeloma• Syngeneic Transplant

Trasplante Syngeneico

Bashey et al, BBMT 20089

Allo Tx

• Graft vs. Myeloma• Syngeneic Transplant• Myeloablative:

• Less disease recurrence -Abandoned

Allo Tx

• Graft vs. Myeloma• Syngeneic Transplant• Myeloablative• Non-Myeloablative

Bjorkstrand et al, JCO 29;22: 3016-3022

Fludarabine 30mg/m2, 2Gy TBI, MMF, CSA

DLI 3 months PR

Allo-RIC vs. Auto Study N Eligib

TXCond GVH

N Tx

Age PFS Surv

Hovon 260 HLA sib 2 Gy TBICSA-MMF

99 54 28%@ 6y22%@ 6y

55%@ 6y55%@ 6y

Gimema 120 HLA sib 2Gy TBI 60 50@ 4y25@ 4y

60@ 4y45@4 y

CTN 700+ HLA sib 2GyTBICSA-MMF

156 43@ 3y46 @ 3y

77@ 3y80@ 3y

EBMT-NMAM

375 HLA-sib Flu 2 Gy TBICSA-MMF

109 22 @8y12@8y

49@ 8y36@ 8y

IFM 284* HLA Sib BU 4 Flu ATGCSA-MTX

65 54 19@5y22@5y

40@ 5y45@5y

PETHEMA

110** HLA-sib Flu-Mel 140 25 52 60%@5y25%@5y

60%@5y60%@5y

* Only B2M >3 and 13q del ** no nCR after Tx1

Allo-RIC vs. Auto Study N Eligib

TXCond GVH

N Tx

Age PFS Surv

Hovon 260 HLA sib 2 Gy TBICSA-MMF

99 54 28%@ 6y22%@ 6y

55%@ 6y55%@ 6y

Gimema 120 HLA sib 2Gy TBI 60 50@ 4y25@ 4y

60@ 4y45@4 y

CTN 700+ HLA sib 2GyTBICSA-MMF

156 43@ 3y46 @ 3y

77@ 3y80@ 3y

EBMT-NMAM

375 HLA-sib Flu 2 Gy TBICSA-MMF

109 22 @8y12@8y

49@ 8y36@ 8y

Blood 2012 119, 6219Blood 2011,;117,6721Lancet Oncol 2011, 12,1195Blood 2013, 121, 5055

Auto-RIC vs. Auto: RelapseHovon Gimema

EBMT

Auto RIC vs. Auto: Survival

Gimema

Hovon

CTN EBMT

EBMT: Myeloma with 13q

PETHEMA:PFS After Allo vs. 2nd Auto in <nCR

Rossinol Blood 2008

OS from the time of first relapse/progression in patients with multiple myeloma treated with auto/RICallo or auto alone.

Gahrton G et al. Blood 2013;121:5055-5063

©2013 by American Society of Hematology

Survival after relapse is Superior in patients undergoing Allogeneic Transplant

Graft vs. Myeloma Optimized?

Tricot G. Blood 87;3 1996 1196-1198.

Lenalidomide?Pomalidomide?Vaccines?

Conclusions• Toxicity of allogeneic Transplant has been

reduced in recent years• With prolonged follow-up the benefit of allo

transplant becomes more apparent.• Allogeneic Transplant is particularly attractive

for poor prognosis patients.• The future:

• Alternative donors• Avoidance of chronic GVHD• Early Allogeneic Transplant• Incorporation of Maintenance Strategies

Case 1• 35 YoF• MM del 17p, IgG• 2012 Auto: PR• Relapse• VDT-PACE: PR• Haplo cord:

Case 2

• MM IgA• ET• Chloroma• Cytarabine-Arac +

Bortezomib• PR• URD Transplant

Tx in 1st remissionNl cytogenetics

Conclusions• Autologous transplant remains the standard

treatment for myeloma• It is well tolerated and may lead to superior

QOL• Cure may be possible in a fraction of

patients• Allogeneic transplantation should be

considered, particularly in patients with adverse prognosis