Managing Risk in advanced-stage HL Andreas Engert, MD Chairman, - - PowerPoint PPT Presentation

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German Hodgkin Study Group Deutsche Hodgkin Studiengruppe Managing Risk in advanced-stage HL Andreas Engert, MD Chairman, German Hodgkin Study Group University Hospital of Cologne Managing risk in advanced stage HL Key issues Background

SLIDE 1

Managing Risk in advanced-stage HL

Andreas Engert, MD

Chairman, German Hodgkin Study Group University Hospital of Cologne

German Hodgkin Study Group

Deutsche Hodgkin Studiengruppe

SLIDE 2

Managing risk in advanced stage HL

Key issues

Background
Advanced Stages
PerspecEves
Summary

SLIDE 3

Stage (Ann Arbor)

Risk factors

IA, IB, IIA IIB IIIA, IIIB IVA, IVB None

Early favorable

Advanced

≥ 3 LK- Areas

Early unfavor- able

Elevated ESR Large Med Mass Extranodal disease

GHSG Risk Allocation for HL

SLIDE 4

2nd NPL

AML NHL Solid tumours

Organ damage

Lung Heart Thyroid

Others

FerElity OPSI FaEgue Psycho-social

Hodgkin Lymphoma

Late side effects a=er treatment

SLIDE 5

GHSG HD9 trial

FFTF by treatment arm

Engert et al; JCO 2009

p <0,001

Years

A (64%) B (70%) C (82%)

Percentage

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

18%

SLIDE 6

Freedom from Treatment Failure 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 12 24 36 48 60 72 Time [months]

p-value 60 months difference A vs. B: 0.009 4.9% 97.5%-CI: [ 0.5%, 9.3%] A vs. C: 0.5 1.1% 97.5% CI: [-3.7%, 5.8%] C vs. B: 0.04 (n.s.) 3.9% 97.5% CI: [-0.5%, 8.2%]

HD15 in advanced HL

Freedom from Treatment Failure (FFTF)

A: 84.4% B: 89.3% C: 85.4%

Engert A et al, Lancet 2012

SLIDE 7

TRM of BEACOPP escalated*

Multivariate model

Age>40 Age>50 ECOG 2 or Karn.<80 Patients TRM rate

2156

0.7 +

1.7

108 0.9 + +

5.6 +

40 13.3 + + + 45 15.0

Wongso et al, JCO 2013 *Pts treated in HD9, 12, 15 (64/3565; 1.9%)

SLIDE 8

UK RATHL: Impact of Bleomycin

PFS for PET-negative patients (ITT)

HR: 1.11 (0.79 – 1.54), p = 0.53

Johnson et al; NEJM 2016

SLIDE 9

Hodgkin Lymphoma

ECHELON-1: modified PFS

Connors et al., NEJM 2017

SLIDE 10

Hodgkin Lymphoma

ECHELON-1: Side effects

A+AVD ABVD Neutropenia (%) 58 45 InfecEon grade ≥3 (%) 18 10 Peripheral neuropathy (PN: all) (%) 67 43 Peripheral neuropathy (PN), grade ≥3 (%) 11 2 Lungtox grade ≥3 <1 3 Neutropenia associated deaths (no G-CSF prophylaxis) 7 9 Lungtox associated deaths 11 13

Connors et al., ASH 2017: A6

SLIDE 11

504 476 438 363 298 207 501 479 459 370 292 227

Pts. at risk

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12 24 36 48 60 Time [months] 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Overall Survival rate

PET-, 4x eBEACOPP PET-, 8/6x eBEACOPP

3-year esEmate 5-year esEmate 8/6x eBEACOPP: 95.9% [94.1-97-7] 95.4% [93.4-97.3] 4x eBEACOPP: 98.7% [97.6-99.7] 97.6% [96.0-99.2] Difference: +2.7 [+0.6-+4.8] +2.2% [-0.3-+4.7] Hazard RaEo 0.36 [0.17 to 0.76], log-rank test p=0.006

Median observaEon Eme 56 months

HD18 for PET-2-negaLve paLents

Overall Survival

Borchmann et al, Lancet 2017

SLIDE 12

Managing risk in advanced stage HL

Key issues

Background
Advanced Stages
PerspecEves
Summary

SLIDE 13

The GHSG perspecLve

HD21: BV in advanced stage HL

2 x BEACOPP esc

End of therapy and residual nodes > 2.5 cm: PET posiEv: Rx PET negaEve: Follow up

Centrally reviewed PET 2 x BrECADD 4x BEACOPP esc 4x BrECADD

SLIDE 14

Nivolumab for r/r cHL

PFS in CheckMate 205 trial

Fanale M et al. ICML 2017

3 4 5 6 7 8 9 100 18 3 6 9 12 15 Probability of PFS PFS (months) 2 1 CR: 22 (19, NE) months PR: 15 (11, 19) months SD: 11 (6, 18) months PD: 2 (2, 2) months

Median (range) follow-up: 18 (1, 27) ms

SLIDE 15

CheckMate 205 Cohort D

Newly Diagnosed cHL

51 untreated advanced stage cHL pts (IIB, III, IV)
Median follow-up 11.1 months (cut-off 31.8.17)
Bleomycin excluded due to potenEal overlapping pulmonary toxicity
Primary EP: G3-5 safety and tolerability
Primary endpoint: safety and tolerability (G3–5 treatment-related AEs)

Max 2 yrs Nivolumab 240 mg IV Q2W Nivolumab 240 mg IV + AVD (N-AVD) Q2W ~8 wks ~22 wks Follow- up/

bservaE
n

Combotherapy

(6 combocycles; 12 doses)

Monotherapy

(4 doses)

SLIDE 16

Nivo-AVD in advanced stage cHL

End of Combotherapy

46/51 paLents had available response data. Response assessed by IWG 2007 criteria

–50 –100 –75 –25 50 75 25

ReducEon from baseline in target lesion (%) PaEents

PET-negaEve

FDG-PET scan at end of therapy or last prior radiographic assessment

Ramchandren et al, ASH 2017: A651

SLIDE 17

Managing risk in advanced stage HL

Key issues

Background
Advanced Stages
PerspecEves
Summary

SLIDE 18

Advanced-stage HL became curable with mulE-agent chemo
B.esc gave 15-20% beoer PFS and 10-15% beoer OS than ABVD
r variants; more hematotox and inferElity
B.esc not to be used in pts >40 ys and poor performance
HD15: 6xB.esc: tumour control 89%, OS 95%
HD18: only 4 cycles B.esc in PET- pts (3y FFTF 94.8%; OS 98.7%)
ECHELON1 showed 4.9% beoer modified PFS for BV-AVD as

compared with ABVD

New trials evaluate targeted therapy including BV (HD21)

and PD1 inhibitors

Advanced stage HL

Summary

SLIDE 19