Is ABVD standard front line therapy in HL?...Advisory Board: Janssen, Abbvie, Astra Zeneca Research:...
Transcript of Is ABVD standard front line therapy in HL?...Advisory Board: Janssen, Abbvie, Astra Zeneca Research:...
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Is ABVD standard front linetherapy in HL?
Guilherme Fleury Perini, MD
Hospital A Beneficência Portuguesa de São Paulo
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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
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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?
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Modern Therapy of HL – BrazilianRegistry
Biasoli I et al Hematological Oncology. 2017;1–7.
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Modern Therapy – Argentina GATLA Trial
Pavlovsky A et al, Br J Haematol 2019
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BEACOPP x ABVD
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BEACOPP is superior in PFS in HL
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BEACOPP is superior in FFP in HL
Viviani et al, NEJM 2012
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Viviani et al, NEJM 2012
BEACOPP x ABVD: FFSP and OS
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ABVD x BEACOPP: Toxicity
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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?
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ABVD x BEACOPP
Make ABVD GreatAgain!
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Is it time to incorporate BV in firstline therapy?
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Echelon-1 Trial Design
Primary Endpoint: mPFSProgression, Death or mPFSmPFS: <CR + Subsequent therapyPET+ = Deauville 3, 4 e 5
Connors JM et al, NEJM 2018
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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
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mPFS by IRC
Connors JM et al, NEJM 2018
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OS in the ITT population
Connors JM et al, NEJM 2018, Supplement
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Subgroup Analysis
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A+ AVD in High Risk Patients
Radford J, ISHL 2018Hutchings M, EHA 2018
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What about PET2+ patients?
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Adverse Events in ECHELON-1
Connors JM et al, NEJM 2018
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On Study Deaths
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G-CSF Prophylaxis for BV-AVD patients
Connors JM et al, NEJM 2018
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G-CSF Prophylaxis in BV-AVD Patients
Radford J, ISHL 2018
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BV-AVD in ES Unf HL: BREACH Trial
Andre M, ISHL 2018
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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
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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
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What to do without Bleomycin?
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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
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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)
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NLPHL
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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
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Advanced Stage NLPHL
• MD Anderson: R-CHOP x Others
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Therapy of NLPHL
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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