Is still ABVD the best chemotherapy regimen in Hodgkin’s lymphoma ? Alessandro Levis Haematology - Alessandria - Italy
Data from the GHSG HD9 trial in advanced stage HL (from Engert et al JCO 27, 4548, 2009) 8 BEACOPP escalated 4 COPP-ABVD (ABVD-like)
The superiority of BEACOPP in terms of disease control has been confirmed also over ABVD and not only over COPP-ABVD 7-years progression free survival 5-years progression free survival (Gianni et al ASCO 2008; abstract 8506) (Federico et al JCO 2009; 27: 805-811) Folluw up updated to June 2010 personal communication
BEACOPP escalated is superior to ABVD in terms of progression free survival BEACOPP ABVD
Not always the most powerful tool is safe and it is the best choice in order to reach long term results
The problem of toxicity Acute toxicity • Haematological • Infections • Toxic deaths in older patients Late toxicity • Secondary MDS/AML • Infertility
Even the baseline version of BEACOPP is highly toxic over 65 years of age data from HD9 elderly 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)
Secondary cancers Data from the GHSG HD9 in advanced stages Arm A: COPP-ABVD Arm B : BEACOPP baseline Arm C BEACOPP escalated (Engert et al JCO 27, 4548, 2009) 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 Rate of FSH abnormal level Rt only 21 % ABVD/EBVP 26 % Alkylating T. 82 % (from van der Kaaij et al JCO 25, 2825-2832, 2007)
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 Canadian survey on women who tried to become pregnant ABVD 1-year pregnancy rate HL survivors 70 % Control women 75 % (from Hodgson et al Hematol Oncol 25, 11-15, 2007)
Different conditions 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)
Early favourable stages: data from the HD10 GHSG trial random 2 ABVD 2 ABVD 4 ABVD 4 ABVD + + + + Rt IF 20 Gy Rt IF 30 Gy Rt IF 20 Gy Rt IF 30 Gy (Engert et al NEJM 2010,363: 640-652)
Different conditions 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)
Early unfavourable stages: data from the HD11 GHSG trial random Less effective More toxic 4 ABVD 4 ABVD 4 BEACOPP b 4 BEACOPP b + + + + Rt IF 20 Gy Rt IF 30 Gy Rt IF 20 Gy Rt IF 30 Gy 30 Gy 20 Gy 5 y. ABVD vs. BEACOPP b FFTF ABVD vs. BEACOPP b - 1,6 % (Cl -3,6; 6,9) - 5,7 % (Cl 0,1;11,3) (Borchman et al ASH 2009, Abs 717)
Different conditions 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)
Data from the GHSG HD9 in advanced stages Arm A: COPP-ABVD Arm B : BEACOPP baseline Arm 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) 7-years progression free survival 7-years overall survival (Gianni et al ASCO 2008; abstract 8506) Folluw up updated to June 2010: personal communication
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 20% ABVD failures that can benefit from BEACOPP 70 % of patients cured with minimal toxicity with 6 ABVD only (Federico et al JCO 2009; 27: 805-811)
A new hypothesis: a strategy based on chemo-sentivity evaluated according to early PET results ? (Gallamini et al. JCO 25, 3746-3752, 2007)
Advanced stage Staging including PET scan Hodgkin lymphoma IIL-HD0801 protocol stage IIB-IV 2 ABVD - PET + 2 ABVD Salvage 2 ABVD IGEV + ASCT - + CT + PET random Rt bulky No Rt
Ongoing GITIL study IIB-IVB or IIA with more than 3 High-risk HL nodal sites, ESR > 50, bulky lesion PET-0 ABVD x2 PET-2 PET-2 +ve HL PET-2 -ve HL escalated BEACOPP x4 ABVD x4 standard BEACOPP x4 Consolidation RxT Consolidation RxT End-therapy PET By courtesy of Gallamini (ASCO 2010)
Ongoing GITIL study FFS according to PET-2 results reported by the local PET centers. Cohort of 158 patients Subgroup of 141 patients with correctly treated stage IIB-IVB disease All patients PET-2 negative PET-2 positive By courtesy of Gallamini (ASCO 2010)
Conclusions 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.
Acknowledgments to all centres and groups cooperating to the studies of the Intergruppo Italiano Linfomi
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