Is still ABVD the best chemotherapy regimen in …...Alessandro Levis Haematology - Alessandria -...
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Alessandro LevisHaematology - Alessandria - Italy
Is still ABVD the best chemotherapy regimen in Hodgkin’s lymphoma ?
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Data from the GHSG HD9 trial in advanced stage HL(from Engert et al JCO 27, 4548, 2009)
4 COPP-ABVD (ABVD-like)
8 BEACOPP escalated
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The superiority of BEACOPP in terms of disease control has been confirmed also over ABVD and not
only over COPP-ABVD
(Gianni et al ASCO 2008; abstract 8506) Folluw up updated to June 2010
personal communication
7-years progression free survival
(Federico et al JCO 2009; 27: 805-811)
5-years progression free survival
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BEACOPP escalated is superior to ABVD in terms of progression free survival
ABVD
BEACOPP
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Not always the most powerful tool is safe and it is the best choice in order to reach long term results
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Acute toxicity • Haematological• Infections • Toxic deaths in older patients
Late toxicity• Secondary MDS/AML• Infertility
The problem of toxicity
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Even the baseline version of BEACOPP is highly toxic over 65 years of age
data from HD9elderly study of the GHSG
COPP-ABVD BEACOPP
N° of patients 26 42
Grade IV leucopaenia 40 % 87 %
Grade IV any toxicity 44 % 87 %
Toxic deaths 8 % 21 %
(from Ballova et al Ann Oncol 16, 124131, 2005)
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Data from the GHSG HD9 in advanced stages
Arm A: COPP-ABVDArm B : BEACOPP baselineArm C BEACOPP escalated
(Engert et al JCO 27, 4548, 2009)
Secondary cancers
MDS - AML
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Male infertility is a problem after both baseline and escalated BEACOPP chemotherapy
(from Sieniawski et al Blood 111, 71-76, 2008)
% %
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Male infertility is a minimal problem with ABVD as compared to COPP-ABVD
(from Kulkarni et al Am J Clin Oncol 20, 354-357, 1997)
% %
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Male infertility evaluated by high FSH levels is highly dependent on alkyilating agents
(from van der Kaaij et al JCO 25, 2825-2832, 2007)
Rate of FSH abnormal level
Rt only 21 %
ABVD/EBVP 26 %
Alkylating T. 82 %
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Amenorrhea is a major problem with BEACOPP escalated treatment
(Berhinger et al JCO 23, 7555-7564, 2005) (Bonadonna et al JCO 22, 2835-2841, 2004)
% %
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Pregnancy rate is not compromised by ABVD chemotherapy
(from Hodgson et al Hematol Oncol 25, 11-15, 2007)
1-year pregnancy rate
HL survivors 70 %Control women 75 %
Canadian survey on women who tried to become pregnant
ABVD
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Early stage (IA and IIA) without any unfavourable factors (bulky disease, more than 3 sites… )
Early stage (IA and IIA) with one or more unfavourable factors
Advanced stage (IIB-IV)
Different conditions
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Early favourable stages: data from the HD10 GHSG trial
(Engert et al NEJM 2010,363: 640-652)
random
2 ABVD+
Rt IF 30 Gy
2 ABVD+
Rt IF 20 Gy
4 ABVD+
Rt IF 20 Gy
4 ABVD+
Rt IF 30 Gy
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No reasons to shift from ABVD to BEACOPP in favourable early stages
Early stage (IA and IIA) with one or more unfavourable factors
Advanced stage (IIB-IV)
Different conditions
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Early unfavourable stages: data from the HD11 GHSG trial
(Borchman et al ASH 2009, Abs 717)
random
4 ABVD+
Rt IF 30 Gy
4 ABVD+
Rt IF 20 Gy
4 BEACOPP b+
Rt IF 20 Gy
4 BEACOPP b+
Rt IF 30 Gy
30 Gy
ABVD vs. BEACOPP b - 1,6 % (Cl -3,6; 6,9)
20 Gy
ABVD vs. BEACOPP b- 5,7 % (Cl 0,1;11,3)
5 y.FFTF
More toxicLess effective
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No reasons to shift from ABVD to BEACOPP in favourable early stages
What strategy is the less toxic between [4 ABVD + 30 Gy I.F. Radiotherapy] and[4 BEACOPPb + 20 Gy I.F. Radiotherapy] ?
Advanced stage (IIB-IV)
Different conditions
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Data from the GHSG HD9 in advanced stages
Arm A: COPP-ABVDArm B : BEACOPP baselineArm C BEACOPP escalated
(Engert et al JCO 27, 4548, 2009)
Superiority of BEACOPP escalated over COPP-ABVD
in terms of both FFTF and OS
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Superiority of BEACOPP over ABVD in terms of FFS but not in terms of OS (Italian IIL study)
(Gianni et al ASCO 2008; abstract 8506) Folluw up updated to June 2010: personal communication
7-years progression free survival 7-years overall survival
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Superiority of BEACOPP over ABVD in terms of FFTF and PFS but not in terms of OS (Italian GISL study)
(Federico et al JCO 2009; 27: 805-811)
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The advantage of BEACOPP over ABVD in terms of PFS seems to be significant only in the unfavourable group of
IPS 3-7 patients (Italian GISL study)
(Federico et al JCO 2009; 27: 805-811)
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A new hypothesis: a BEACOPP strategy limited to patients candidate to become ABVD poor-responders
(Federico et al JCO 2009; 27: 805-811)
70 % of patients cured with minimal toxicity with 6 ABVD only
20% ABVD failures that can benefit from
BEACOPP
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(Gallamini et al. JCO 25, 3746-3752, 2007)
A new hypothesis: a strategy based on chemo-sentivity evaluated according to early PET results
?
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+
random
Rt bulky No Rt
stage IIB-IV
Staging including PET scan
2 ABVD
- PET
2 ABVD
Salvage IGEV + ASCT
- CT + PET +
2 ABVD
Advanced stage Hodgkin lymphoma
IIL-HD0801 protocol
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ABVD x2
escalated BEACOPP x4ABVD x4
High-risk HL
PET-2
standard BEACOPP x4
End-therapy PET
PET-2 +ve HL PET-2 -ve HL
IIB-IVB orIIA with more than 3 nodal sites, ESR > 50, bulky lesion
Ongoing GITIL study
PET-0
Consolidation RxT Consolidation RxT
By courtesy of Gallamini (ASCO 2010)
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FFS according to PET-2 results reported by the local PET centers.
Cohort of 158 patients correctly treated
Subgroup of 141 patients withstage IIB-IVB disease
All patients PET-2 negative PET-2 positive
Ongoing GITIL study
By courtesy of Gallamini (ASCO 2010)
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No reasons to shift from ABVD to BEACOPP in favourable early stages
What strategy is the less toxic between [4 ABVD + 30 Gy I.F. Radiotherapy] and[4 BEACOPPb + 20 Gy I.F. Radiotherapy] ?
BEACOPP is more effective than ABVD in terms of PFS, but not OS, and front line ABVD escalated strategies have to be considered for the future.
Conclusions
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Acknowledgments to all centres and groups cooperating to the studies of the
Intergruppo Italiano Linfomi