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Alessandro LevisHaematology - Alessandria - Italy
Is still ABVD the best chemotherapy regimen in Hodgkin’s lymphoma ?
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
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
BEACOPP escalated is superior to ABVD in terms of progression free survival
ABVD
BEACOPP
Not always the most powerful tool is safe and it is the best choice in order to reach long term results
Acute toxicity • Haematological• Infections • Toxic deaths in older patients
Late toxicity• Secondary MDS/AML• Infertility
The problem of toxicity
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)
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
Male infertility is a problem after both baseline and escalated BEACOPP chemotherapy
(from Sieniawski et al Blood 111, 71-76, 2008)
% %
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)
% %
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 %
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)
% %
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
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
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
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
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
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
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
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
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)
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)
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
(Gallamini et al. JCO 25, 3746-3752, 2007)
A new hypothesis: a strategy based on chemo-sentivity evaluated according to early PET results
?
+
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
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)
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)
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
Acknowledgments to all centres and groups cooperating to the studies of the
Intergruppo Italiano Linfomi
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