Hodgkin Lymphoma

Question 1

Ann Arbor Classification of Hodgkin Lymphoma

Answer 1

Question 2

Demografics

Answer 2

• Ca. 2,500 Neuerkrankungen/a in DE
• 2 „Altersgipfel“: 15-30 Jahre und > 60 Jahre
• Nicht schmerzhafte Lymphknotenschwellung
• Unspezifische Symptome: Leistungsabfall, B-Symptome
• Hohe Heilungsrate > 90 % Langzeitüberleben

Question 3

WHO Classification of HL

Answer 3

Question 4

German Hodgkin Lymphoma Classification

Answer 4

More than 3 different anatomical sites : unfavourable
Several sites in the mediastinum is still considered as one site

Question 5

Evolution der RT Felder bei HL

Answer 5

Question 6

Late effects of Treatment in HL

Answer 6

Secondary Neoplasia: AML, NHL, Solid tumours
Organ damage: Lung, Heart, Thyroid
Others: Fatigue, Fertility

Question 7

Frühe Stadien: Early favourable HL - Seminal study GHSG HD10

Answer 7

Question 8

GHSG HD10 – results

Answer 8

Question 9

Frühe Stadien: PET-stratifizierte Therapie

Answer 9

Question 10

Frühe Stadien: PET-stratifizierte Therapie bei HL – HD16

Answer 10

Question 11

Intermediäre Stadien: HD11

Answer 11

20 oder 30 Gy ?

Question 12

Intermediäre Stadien: HD11 Results

Answer 12

This final analysis shows that 4 cycles of ABVD 30 Gy of IFRT leads to equivalent results as 4 cycles of BEACOPP-baseline followed by either 30 or 20 Gy of IFRT. However, four cycles of ABVD followed by 20 Gy of IFRT were inferior to the other three arms, implying that a reduction of IFRT dose from 30 to 20 Gy is only possible when combined with a more intensive chemotherapy regimen than ABVD.

Question 13

Intermediäre Stadien: HD14

Answer 13

4x ABVD versus
2x BEACOPPeskaliert + 2x ABVD ?

30 Gy IFRT in both arms.

Question 14

Intermediäre Stadien: HD14 Results

Answer 14

Intensified chemotherapy with two cycles of BEACOPP escalated followed by two cycles of ABVD followed by IFRT significantly improves tumor control in patients with early unfavorable HL.

Question 15

Intermediäre Stadien : HD17 bei Hodgkin Lymphom in mittleren Stadien

Answer 15

Question 16

Intermediäre Stadien : HD17 results

Answer 16

Question 17

Zusammenfassung für Frühstadien

Answer 17

2 x ABVD + 20 Gy ISRT für early-favorable
Kein Verzicht auf RT bei early-favorable

2 x BEACOPPesk+ 2 x ABVD (+/-30 Gy ISRT) für early-unfavorable
Bei early-unfavorable: Verzicht auf RT möglich
Interim-PET als wesentlicher Prädiktor des Ansprechens

Weitere Stratifizierung?/(De-)Eskalation?

Question 18

ESMO 2018 Hodgkin Lymphoma (Early stage)

Answer 18

Question 19

ESMO 2018 Hodgkin Lymphoma (Intermediate stage)

Answer 19

Question 20

Fortgeschrittene Stadien : HD9

Answer 20

In der HD9-Studie wurden 4 x COPP/ABVD, 8 x BEACOPP basis und 8 x BEACOPPeskaliert miteinander verglichen. Anschließend wurde gegebenenfalls bestrahlt (30 Gy Bulk, 40 Gy Residualtumor)

BEACOPP intensiviert eindeutig besser (freedom from treatment failure and OS)
Incidence of acute toxicity increased with increased-dose BEACOPP

Question 21

Fortgeschrittene Stadien : HD15

Answer 21

In der HD15-Studie wurden acht Zyklen BEACOPPeskaliert mit sechs Zyklen BEACOPPeskaliert und acht Zyklen BEACOPP 14 verglichen. Nach Abschluss der Chemotherapie wurde eine PET-Untersuchung durchgeführt, PET-positive Reste größer als 2,5 cm wurden bestrahlt.

Question 22

Fortgeschrittene Stadien : HD15 Results

Answer 22

6x BEACOPP(escalated) followed by PET-guided RT was more effective in terms of freedom from treatment failure and less toxic than 8x BEACOPP(escalated). 6x BEACOPP(escalated) should be the treatment of choice for advanced stage HL. PET done after chemotherapy can guide the need for additional radiotherapy in this setting.

Question 23

Fortgeschrittene Stadien : HD18

Answer 23

investigated whether metabolic response determined by PET after 2 cycles of standard escalated regimen eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for PET-2-positive patients and reducing it for PET-2-negative patients.
Patients with positive PET-2 receive 6 × eBEACOPP
Patients with negative PET-2 were randomly assigned to 6 × eBEACOPP (standard) or 4 × eBEACOPP (experimental)

Question 24

Fortgeschrittene Stadien : HD18 Results

Answer 24

PET-2 negativity allows reduction to only four cycles of eBEACOPP without loss of tumour control. PET-2-guided eBEACOPP provides outstanding efficacy for all patients and increases overall survival by reducing treatment-related risks for patients with negative PET-2.

HD21 pending…

Question 25

PD1 Inhibition in classical Hodgkin Lymphoma

Answer 25

Patients with cHL show high frequency of 9p24.1 alterations and overexpression of PD-L1 and PD-L21
Tislelizumab is a humanized immunoglobulin (Ig) G4 monoclonal antibody that binds to the extracellular domain of human PD-1 with high specificity and affinity to block binding to both PD-L1 and PD-L2. Unlike other anti–PD-1 antibodies, tislelizumab has a mutated Fc region and is specifically engineered to minimize FcγR binding on macrophages, thereby abrogating antibody-dependent phagocytosis, which is a potential mechanism of T-cell clearance and resistance to anti–PD-1 therapy.

Question 26

Brentuximab vedotin in HL

Answer 26

is an anti-CD30 antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE). Following binding to CD30, brentuximab vedotin is rapidly internalized and transported to lysosomes where MMAE is released and binds to tubulin, leading to cell cycle arrest and apoptosis

Question 27

Summary for advanced stage HL

Answer 27

eBEACOPP (better in terms of PFS and OS) vs ABVD, however more hematoxicity and infertility.
Only 4x eBEACOPP is needed in PET-negative pts
ECHELON-1 Trial showed that BV-AVD was better than ABVD.
RT only for PET-positive residual (>1.5 cm)

Question 28

ESMO 2018 Hodgkin Lymphoma (Advanced stage)

Answer 28

Question 29

Summary for of studies randomising RT

Answer 29