Linfoma de Hodgkin

Enfermedad en Relapso/Recaída
Daniel Enriquez, MD, Msc
Médico Oncólogo
PhD(c) at Kagoshima University
Disclosure
• Nothing to disclose.
• I’m a student again 
“It has been gratifying to see Hodgkin’s disease change from a largely incurable
condition to a mostly curable one during my professional lifetime.”

Vincent DeVita, 2003

Introduction(I)

N=1429 (1992-2009)

13 Relapse (Early-2.4%,
Late-10.6%) – 60%
% survival

Primary Refractory
2% (During Treatment -
<3mo) – 50% survival

Glimelius, I. American Journal of Hematology, 90(12), 1128–1134.

 Introduction(II)
FFS – 5 years

<20y: 80%
20-60y: 70%
>60y: 50%

Henderson (2018). Cancer, 124(1), 136–144.

Tumor Microenviroment
• 1% of Tumor population
• NF-kb (CD30-40)
• Brentuximab Vedotin: anti-
CD30 conjugated to
monomethyl auristatin E
(MMAE)

Steidl C et al. JCO 2011 Steidl et al. Blood 2018

Role of HSCT in R/R HL

Schmitz, et al. Lancet. 2002; Advani, et al. Blood. 2021 Apr 7;

Moskowitz AJ. ASH 2019.
Pre-transplant PET – as prognostic factor
for R/R HL

Schmitz, et al. Lancet. 2002; Lynch, et al. Lancet. 1993 Moskowitz AJ et al. Blood
2010;116:4934-7
 Cht as second line: All similar!

1. Moskowitz CH et al. Blood 2012;119:1665-70; 2. Josting A et al. Annals of Oncology 2002;13: 1628-35; 3. Bartlett NL et al. Annals of Oncology 2007;
18:1071-9; 4. Baetz T et al. Annals of Oncology 2003;14:1762-7; 5. Santoro A et al. Haematologica 2007; 92:35-41
PET-Adapted 2L: Yes, also in R/R

EFS 70%

60%

40%

Moskowitz CH et al. Blood 2012;119:1665-70

PET-Adapted 2L: BV and augICE

Moskowitz AJ et al. Blood 2017

Sequential BV->Cht as second line
BV-Nivolumab

Alex F. Herrera et al. Blood 2018;131:1183-1194

BV+Nivo in 1st Relapse HL

Advani et al. Blood 2021

 PET-neg vs Regimens

1Moskowitz AJ et al. Blood 2010;116:4934-7; 2Moskowitz AJ, et al. ASH 2019; 3Herrera et al Ann Oncol 2018; 4LaCasce et al. Blood 2018; 5Stamatoullas et al,
ASH 2019; 6Kersten et al. Haematologica 2020; 7Garcia-Sanz, et al. Ann Oncol 2019; 8Cole, et al. Lancet Oncol 2018; 9Advani, et al. Blood 2021; 10Santoro, et
al. Blood Advances 2020
Post-transplant BV maintenance

• AETHERA: Phase III study 5-Year PFS Rates

evaluating post-transplant BV=59% Placebo=41%
maintenance BV for higher risk HR=0.521
patients
• Risk factors: Relapse within 1
year of initial treatment,
primary refractory disease,
extranodal disease
• 329 patients received
brentuximab vedotin (BV)
(n=165) or placebo (n=164)

Moskowitz CH, et al. Lancet 2015;385:1853-62 Moskowitz CH, et al. ISHL 2018
Who really benefit from BV maintenance?

Risk Factors
•Primary-refractory HL or relapse <12 months
from completion of frontline therapy
•PR or SD as best response to salvage therapy
pre-ASCT
•≥2 previous salvage therapies
•Extranodal disease at pre-ASCT relapse
•B symptoms after failure of frontline therapy

Moskowitz CH, et al. Lancet 2015;385:1853-62 Moskowitz CH, et al. ISHL 2018
Immunotherapy for R/R HL

Younes et al. Lancet Onc 2016

Immunotherapy: a new paradoxical
paradigm

Chen et al. Blood 2019

Pembrolizumab + GVD

Moskowitz, A. J. (2021 Journal of Clinical Oncology, 39(28), 3109–3117.

Pembrolizumab + GVD

Moskowitz et al. JCO 2021

Pembrolizumab + GVD
• ORR 100%
• Median follow-up post AHCT: 13.5 months
• PET-negative rate: 95%
• 30/36 (83%) proceeded to AHCT after 2 cycles

Moskowitz, A. J. (2021 Journal of Clinical Oncology, 39(28), 3109–3117.

BV-nivo vs BV-ipi-nivo in PD-1 naïve
relapsed/refractory HL

Diefenbach et al. Lancet Heme 2020

Pembro vs BV as monotherapy for R/R HL

Kuruvilla, J (KEYNOTE-204): The Lancet Oncology, 22(4), 512–524.

Further 3rd line
Treatments
Camidanlumab tesirine
CAR-T CD30
• 41 patients at 2 centers
• ORR 72%
• CR: 59%
• 1 year PFS: 36%
PD-1 inhibitor plus decitabine active in
relapsed/ref HL

Nie et al. JCO 2019

AFM13 plus pembrolizumab in PD-1 naïve
rel/ref HL

Bartlett et al. Blood 2020

Summary
• PET-guided in R/R Therapy.
• Early-relapse: Pembro-GVD vs
BV-Nivo
• Late-relapse: Cht
• High-risk patients: BV
maintenance

Driessen, J. Blood 2021.

Many thanks.

Enriquezv.dj@gmail.com