is abvd standard front line therapy in hl?...advisory board: janssen, abbvie, astra zeneca research:...
TRANSCRIPT
Is ABVD standard front linetherapy in HL?
Guilherme Fleury Perini, MD
Hospital A Beneficência Portuguesa de São Paulo
Disclosures
Speaker’s Bureau: Janssen, Roche, Takeda, Abbvie, BMS
Educational Support: Janssen, Takeda, Roche, Abbvie
Advisory Board: Janssen, Abbvie, Astra Zeneca
Research: Janssen, Millenium, Merck, Alnylam
Slides will be presented in English for bettercomprehension of invited speakers
Topics to be discussed
• Modern results of HL therapy
• Is there still room for the debate ABVD x BEACOPP?
• Is it time to incorporate BV in first line therapy?
• What to do without bleomycin?
• NLPHL – ABVD x R-CHOP?
Modern Therapy of HL – BrazilianRegistry
Biasoli I et al Hematological Oncology. 2017;1–7.
Modern Therapy – Argentina GATLA Trial
Pavlovsky A et al, Br J Haematol 2019
BEACOPP x ABVD
BEACOPP is superior in PFS in HL
BEACOPP is superior in FFP in HL
Viviani et al, NEJM 2012
Viviani et al, NEJM 2012
BEACOPP x ABVD: FFSP and OS
ABVD x BEACOPP: Toxicity
ABVD x BEACOPP: My POV
• ABVD x 6 – Highly effective, acceptable toxicity
– 30-35% patients fail*, app. 50% are cured with HD+ ASCT
– Undertreatment of 1/3 patients
• BEACOPPesc x 6 – Cures more patients in first line
– OS benefit in 5% (NNT ~ 20)
– More acute and late toxicity
– Overtreatment of 2/3 of patients
• PET-adapted therapies + New Drugs: – Is it worth increasing chemo intensity?
• Is it feasible in Brazil?– Bleomycin and Procarbazine availability
– G-CSF support/Outpatient support
– Are we experienced with BEACOPP?
ABVD x BEACOPP
Make ABVD GreatAgain!
Is it time to incorporate BV in firstline therapy?
Echelon-1 Trial Design
Primary Endpoint: mPFSProgression, Death or mPFSmPFS: <CR + Subsequent therapyPET+ = Deauville 3, 4 e 5
Connors JM et al, NEJM 2018
Estudo Avaliação de Resposta Endpoint Primário Endpoint Primário
NCRI, UK Cotswold criteria PFS Morte, progressão ou recaída
Intergroup Italiano Linfomi
Cotswold criteria FFS Morte, progressão, recaída ou <CR @EOT
ECOG E2496 -- FFS Morte, progressão ou recaída
GHSG 12 Cotswold criteria FFS Morte, progressão ou recaída ou resgate após não atingir CR
GHSG 15 -- FFTF Morte, progressão, recaída, resgate após resposta incompleta
GHSG 18 Criterios de Deauvillecom PET negativo <2
PFS Morte, progressão ou recaída
Intergruppo Italiano Linfomi
RECIST FFP Morte, progressão ou recaída, ou <CR @EOT
Intergruppo Italiano Linfomi HD2000
Cotswold criteria FFS Morte, progressão ou recaída, ou <CR @EOT
EORTC 20012 RECIST EFS Morte, progressão, recaída, descontinuação precoce, sem Cr/Cru @EOT
Lysa H34 RECIST EFS Morte, progressão, recaída, descontinuação precoce, sem Cr/Cru @EOT
RATHL Criterios de Deauvillecom PET negativo <3
PFS Morte, progressão ou recaída
ECHELON-1 Cheson 2007Deauville 1-2
mPFS* Modifed PFS
mPFS by IRC
Connors JM et al, NEJM 2018
OS in the ITT population
Connors JM et al, NEJM 2018, Supplement
Subgroup Analysis
A+ AVD in High Risk Patients
Radford J, ISHL 2018Hutchings M, EHA 2018
What about PET2+ patients?
Adverse Events in ECHELON-1
Connors JM et al, NEJM 2018
On Study Deaths
G-CSF Prophylaxis for BV-AVD patients
Connors JM et al, NEJM 2018
G-CSF Prophylaxis in BV-AVD Patients
Radford J, ISHL 2018
BV-AVD in ES Unf HL: BREACH Trial
Andre M, ISHL 2018
BV-AVD in Unf ES: BREACH Trial
• 170 patients enrolled
PET Responses after 2 cycles n(%)
BV-AVDN=113
ABVDN=57
Negative 93 (82.3) 43 (75.4)
90% confidenceinterval
(75,3% ; 88.0%) (64.3% ; 84.5%)
Andre M, ISHL 2018
Is it time to incorporate BV?
• BV-AVD is not for everyone!
– High risk: Stage IV and
>1 EN sites
– G-CSF Prophylaxis
– Toxicity
– Not-cost effective
• Unfortunately, Bleo Shortage is “forcing” BV-AVD in a lot of patients
Huntington SF, ASCO 2018
What to do without Bleomycin?
Bleomycin Shortage: What thedata tells us?
• Favorable ES HL(GHSG HD13)– FFTF: 89,2% AVD x 92,3% ABVD– PFS: 89,6% AVD x 92,9% ABVD– OS: 97,6% AVD x 96,2% ABVD
• Unfavorable ES HL– No published data I am aware of
on Bleo Omission– Waiting for results of BREACH
• EA: – Omission of bleomycin if PET2neg– BV in high risk patients
cHL: How I treat my patients in 2019?
• Early Stage Favourable– 2x ABVD + 20Gy (GHSG HD10)– 2x AVD + 30 Gy (GHSG HD13)
• Early Stage Unfavourable– 4x ABVD + 30Gy– 2x ABVD + 2x AVD + 30Gy– 4x BV-AVD + 30 Gy
• Advanved Stage: – 6x ABVD
• Bleo Omission if PET2neg• No GCSF Support
– I consider BV-AVD in High Risk Patients (Stage IV or >1 EN sites)
– As per now, I am not escalating therapy based in PET2+ results (42% PFS in ECHELON-1, 64% PFS in SWOG S016, 58-72% in GATLA, 70% PFS in HD0801, 63% GITIL)
NLPHL
Important Features
• Very few patients with B Symptoms
• Low mediastinal involvement (7%)
• Higher risk of transformation for T-cell/Histiocyte DLBCL with abdominal involvement:– Transformation risk: 7, 15 e 31% in 10, 15 e
20y
Advanced Stage NLPHL
• MD Anderson: R-CHOP x Others
Therapy of NLPHL
Conclusions
• ABVD remains standard first line therapy for cHL– PET-2 Neg: Continue with AVD– PET-2 Pos: No SOC. eBEACOPP an option
• BV-AVD marginally superior to ABVD regardingmPFS: – Consider in Stage IV and EN sites>1– Higher toxicity/GCS-F Needed– Not cost effective
• A(B)VD should be the backbone for studyincorporating new agents
