Post on 27-Jan-2016
transcript
APL meeting, Rome, Italy. Sept. 25 2009
Salvage Therapy with Chemotherapy- or Arsenic Trioxide-based Regimens for Acute Promyelocytic Leukemia in
First Relapse.
P. Montesinos, J. Esteve, E. Vellenga, C. Rivas, S. Brunet, P. Montesinos, J. Esteve, E. Vellenga, C. Rivas, S. Brunet, M. Arnan, J. D. González, P. Sánchez, J. Díaz-mediavilla, M. Arnan, J. D. González, P. Sánchez, J. Díaz-mediavilla, A. Verdeguer, L. Escoda, E. Amutio, V. Rubio, I. Pérez, R. A. Verdeguer, L. Escoda, E. Amutio, V. Rubio, I. Pérez, R.
Guàrdia, J. Bueno, B. Lowenberg, and M.A. Sanz. On Guàrdia, J. Bueno, B. Lowenberg, and M.A. Sanz. On behalf behalf of the PETHEMAof the PETHEMA, HOVON and GATLA Groups, HOVON and GATLA Groups
Background
• Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL).
• The efficacy and safety of salvage therapy using ATO-based approaches compared with chemotherapy-based regimens is not well established.
Objectives
• We analyze the clinical outcome of 110 APL patients in first relapse who received salvage therapy with chemotherapy- or ATO-based regimens.
Patients and Methods
• From June 1997 to May 2009, 110 of 1,225 patients included in three subsequent PETHEMA trials (LPA96, LPA99 & LPA2005) relapsed after front-line therapy.
• Salvage therapy:
• 67 patients (61%) CT-based regimens.
• 43 patients (49%) ATO-based regimens.
Salvage therapy: CT-based regimens
• Induction with ATRA plus mitoxantrone plus cytarabine (n=46), plus etoposide (n=7), or other anthracycline-based regimens (n=14).
• Consolidation with one cycle of chemotherapy followed by SCT.
• Patients not eligible for SCT received one additional consolidation cycle with or without maintenance therapy.
Salvage therapy: ATO-based regimens
• Induction with ATO (0.15 mg/kg) ± ATRA (45mg/sqm) until CR.
• Consolidation with one cycle of ATO (5d x 5w) plus ATRA (15d), followed by SCT.
• Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without gemtuzumab ozogamicin or other agents.
Patient characteristics (1)
CharacteristicTotal
(n=110)
CT-based(n=67)
ATO-based (n=43)
P
Age, median (range) 40 (2-81) 37 (2-73) 42 (10-81) NS
Gender, % Male 63 63 63 NS
FAB, % M3V 33 (30) 19 (28) 14 (33) NS
BCR3 isoform, % 58 (54) 23 (53) 23 (55) NS
Secondary APL, % 6 (5) 3 (4) 3 (7) NS
ATO-Based group (n=43)
42%
49%
9%
CT-Based group (n=67)53%44%
3%
High-riskIntermediate-riskLow-risk
Relapse-risk group at APL diagnosis
ATO-Based group (n=43)
33%
55%
12%
CT-Based group (n=67)
34%
53%
13%
Molecular RelapseClinical RelapseCNS Relapse
Type of relapse
Patient characteristics (2)
CharacteristicTotal
(n=110)
CT-based(n=67)
ATO-based (n=43) P
Early relapse
(<18 months), N (%)54 (49) 40 (60) 14 (33) 0.01
Follow-up in months,
median (range)
38
(2-134)
62
(6-134)
18
(2-53)<0.01
Results: Induction therapy
7% 5%
88%
12%4%
84% DeathResistanceCR2
ATO-Based group (n=43)
CT-Based group (n=67)
P = 0.49
Results: Molecular Remission
9%
91%
21%
79%PCR positivePCR negative
ATO-Based group (n=38)
CT-Based group (n=56)
P = 0.13
ATO-Based group (n=38)
50%11%
39%
CT-Based group (n=56)36%
25%
39%
Auto-SCTAllo-SCTNon-SCT
Post-remission therapy
*4 mobilization failures, 7 early relapses before planned SCT
*No mobilization failures, 6 early relapses before planned SCT
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
babi
lity
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
babi
lity
Results in the overall seriesaccording to
salvage therapyOS
RFS
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Prob
abili
ty
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Prob
abili
ty
63%
44%
P = 0.05
ATO-based (n=43)
CT-based (n=67)
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
babi
lity
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
babi
lity
DFS
34%
33%
P = 0.51
ATO-basedCT-based
37%
34%
P = 0.61
ATO-based (n=38)CT-based (n=56)
OS after Auto-SCTaccording to salvage therapy
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
ba
bili
ty
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
ba
bili
ty
87%
60%
P = 0.03ATO-based (n=19)
CT-based (n=20)
OS after Allo-SCTaccording to salvage therapy
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
ba
bili
ty
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120 132 144
Months
Pro
ba
bili
ty
100%
56%
P = 0.15ATO-based (n=4)
CT-based (n=14)
OS in patients not receiving SCTaccording to salvage therapy
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120
Months
Pro
ba
bili
ty
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60 72 84 96 108 120
Months
Pro
ba
bili
ty
38%
26%
P = 0.98
ATO-based (n=15)
CT-based (n=22)
Concluding remarks
• High rates of second CR with either ATO (88%) or chemotherapy regimens (84%).
• The 2-year DFS and RFS were similar with both approaches.
• An apparent benefit in terms of OS was observed in the ATO-based group (P=0.05), especially in patients undergoing SCT.
• A longer follow-up is required in the ATO-based group to confirm these results.
Participating Institutions
H.U. La Fe, ValenciaH. Central, AsturiasH.J. Canalejo, CoruñaH. General, Jerez H. Clinic, BarcelonaH.C. S. Carlos, MadridH. Clínico, ValenciaH. Cruces, BaracaldoH. 12 Octubre, MadridH.C.U. SalamancaH. Son Dureta, MallorcaH.U. P. del Mar, CádizH. Insular, Las PalmasC.H. Xeral-Calde, LugoH. General, AlicanteH.S.P.Alcántara, Cáceres
H. Carlos Haya, MálagaH.C.U. SantiagoH. Reina Sofia, CórdobaH. Dr. Peset, ValenciaH. San Pau, BarcelonaH. Joan XXIII, TarragonaH.U. V. D'Hebron, BarcelonaC.H. LeónH. Navarra, PamplonaH.C. ValladolidH. G. AlbaceteH. M. Valdecilla, SantanderH.U. V. D'Hebron (Inf), BarnaH. La Princesa, Madrid
H.U. G. Trias i Pujol, Barna
H. Dr. Negrin, Las PalmasH. M-Infantil, Las PalmasH. Basurto, BilbaoH. R. Hortega, ValladolidH.C.U. ZaragozaH.G.E. Ciudad de JaénH.U. V. Victoria, MálagaH.General, CastellónH.U. V. Arrixaca, MurciaH. Montecelo, PontevedraF. Jiménez Díaz, MadridC.H. de SegoviaH. Meixoeiro, VigoH. Severo Ochoa, LeganésH.G. Murcia
H. San Jorge, HuescaH. Ramón y Cajal, Madrid
Participating Institutions
Fundaleu, Buenos Aires
H. Rossi, La PlataH. General San Martín, La Plata
H. General San Martín, ParanáI. Trasplante de Médula Ósea, La Plata
H. Clemente Álvarez, Rosario
GATLA (Argentina)
I. P. de Hematología, ParanáH. de Clínicas, Buenos Aires
H.U. del Aire, MadridH. del Mar, Barcelona H. Dr. Trueta, GeronaH. Niño Jesús, Madrid
H.G. Valencia
F. Hospital, Brno (Czec Rep.)
H.U. Arrixaca (Inf), Murcia
H. Xeral-Cies, Vigo
H. Txagorritxu, VitoriaH. General (Inf), AlicanteH. Río Carrión, PalenciaH. C. Haya (Inf), MálagaH. P. Asturias, A. HenaresH. Mutua, Terrasa
H. N.S. Sonsoles, Ávila
H. Sta María Rosell, CartagenaH. San Rafael, MadridH. Virgen de la Cinta, TortosaH. C. Haya (Inf), Málaga
H. Virgen del Rocío, Sevilla
H. Maciel, Montevideo (Uruguay)
HOVON (The Netherlands)
H. La Paz (Inf), Madrid
H.C. San Carlos (Inf), MadridI.C.O., Hospitalet de Llobregat
H.U. La Fe (Inf), ValenciaSHOP (Spain)