eha-tsh hematology tutorial on lymphoma · epidemiology new cases 2.4.-2.5/100,000 persons (eu and...

Hodgkin Lymphoma: Diagnosis

and Treatment (First Line and

Relapsed Disease

Speaker: Pervin Topcuoglu

EHA-TSH Hematology Tutorial

on Lymphoma

İzmir, Turkey

April 6-7, 2019

I have no actual or potential conflict of interest

in relation to this presentation

Learning Objectives

‒ the morphological and clinical features

‒ the staging work-up and apply the Lugano

classification to patients with Hodgkin lymphoma.

‒ the risk stratification prior to the treatment

‒ the treatment in patients with newly diagnosed HL

and in those with relapse/refractory HL

Content

‒ History

‒ Definition

‒ Epidemiology

‒ Subtypes

‒ Etiology

‒ Presentation

‒ Diagnosis

‒ Management

‒ Follow-up

‒ Summary and Future

History

Definition ‒ A type of malignant

lymphoma

‒ Germinal B center or Post-GBC

‒ Dorothy Reed and Carl Sternberg first described the malignant cells of HL-called as Reed Sternberg cells -Owl

Eyes appearance

‒ The first cancer could be successfully treated by radiation therapy and also combination with chemotherapy (ChT)

Epidemiology

New cases 2.4.-2.5/100,000 persons (EU and US data) male, 2.9; female, 2.2

HL most frequently diagnosed in patients 20-34 yrs of age, older than 55 yrs of age

Increased incidence in industrialized countries

Nodular sclerosis subtype associated with high standard of living

Hodgkin Lymphoma Cancer Stat Facts. 2018. https://seer.cancer.gov/statfacts/html/hodg.html.

Median age at

diagnosis

39

0%

10%

20%

30%

40%

<20

20-3

4

35-4

4

45-5

4

55-6

4

65-7

4

75-8

4

>84

Perc

ent

o D

eath

s

Age

Median age at death

67

Estimated New Cases in 2018 8,500

% of All New Cancer Cases 0.5%

Estimated Death in 2018 1,050

% of All Cancer Deaths 0.2 %

Percent Surviving 5

years

86.6 %

2008-2014

0,00

0,50

1,00

1,50

2,00

2,50

3,00

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015N

um

ber

Per

100,0

00

Pers

ons

Years New Cases Death-US

Epidemiology

Hodgkin Lymphoma Cancer Stat Facts. 2018.

https://seer.cancer.gov/statfacts/html/hodg.html.

Histological Subtypes as

WHO classification

Type Proportion of All HL

Classical HL Nodular sclerosis classical HL

Mixed cellularity classical HL

Lymphocyte rich classical HL

Lymphocyte depletion HL

95 % 70 %

20-25 %

5 %

1-2 %

Lymphocyte predominant nodular,

HL 5 %

Swerdlow, SH IARC Press. 2008. Swerdlow, SH, et al. Blood.

2016;127(20):2375-2390 Teras. CA Cancer J Clin. 2016.

Risk Factors

‒ High socioeconomical status: NS type

‒ Low socioeconomical status: MC and LD

‒ EBV: MC ve LD

‒ HIV and other immunosupresive situation

‒ Familial history: 3-5 fold

Presentation

‒ Supradiaphragmatic LAP

• Cervical

• Anterior mediastinal

• Supraclavicular

• Axillary: 10-20 %

‒ Inguinal LAP (less) 6-12 %

Painless LAP: 70 %

60-80%

Presentation

‒ 1/3rd of the patients:

• Fever

• Drenching night sweats

• Weight loss (more than 10 % of BW within 6 months)

‒ Fatigue

‒ Chronic pruritus which may be early sign (15 %)

‒ Pain localized to the site of involved LAP that is precipitated by the consumption of alcohol.

B symptoms

Presentation

‒ Most commonly EN involvement:

• Spleen

• Lungs

• Liver

• Bone marrow

Other Presentations

‒ Skin lesions: • Ichthyosis, acrokeratosis, urticaria, erythema multiforme,

erythema nodosum, necrotizing lesions, hyperpigmentation, skin

infiltration

‒ CNS involvement is rare, but paraneoplastic

neurological syndroms such as cerebellar

degeneration

‒ Nephrotic syndrome

‒ Hypercalcemia

‒ Anemia, thrombocytopenia, leukocytosis

‒ Chest pain, bronchial obstruction, abdominal pain,

spinal cord compression, and peripheral edema

Diagnosis

‒ Excisional LN biopsy

‒ If excision not feasible core-needle biopsy may

suffice

‒ FNA is inadequate for initial diagnosis

Histological and IHC

Features ‒ HL originated from GCB or post-GBC cells

‒ Classical HL includes Reed-Sternberg Cells(RS) (CD30+, CD15+ variable, PAX5+)

• RS cells: Large binucleated or

multinucleated cells with pale chromatin, distinct nuclear membrane, single prominent eosinophilic, inclusion-like nucleolus in each nuclear lobe, and abundant amphophilic cytoplasm

‒ Surrounding inflammatory cells

RS cells 0.1-2% of

total tumor cells

Nodular Lymphocyte-Predominant Hodgkin Lymphoma ‒ Macronodular proliferation are

composed of scattered neoplastic cells: lymphocyte- predominant (LP) cells.

‒ IHC pattern: CD20+, PAX-5+, and CD79a+

‒ In contrast to RS cells, CD15- and CD30-, but OCT-2+ and BOB.1+ .

‒ The origin is GBC: BCL-6+ but usually CD10neg

‒ 50% of the pts are EMA+, variably express IRF4/MUM1.

‒ EBERneg and LMP-1neg

Evaluation and Staging

‒ WBC

‒ RFT, albumin and LFT

‒ ESR and C-RP

‒ PA X-Ray

‒ Hepatitis tests (B and C) and HIV screening

‒ PET/CT*

‒ BM biopsy is no longer indicated in PET/CT

available

‒ MRI and PET/MRI in selected patients

*Prior to ChT or surgery, gross tumor volume and planning target volume should be defined.

tRoutine BM bx is not required if the PET scan (-) or displays homogenous pattern of BM

uptake. BM may be assumed to be involved if the PET scan displays multifocal (≥3) skeletal

lesions

Evaluation and Staging

‒ Prior to treatment: • Cardiac evaluation (ECO or MUGA)

• If necessary, Pulmonary function tests

• Thyroid tests

• Reproductive counseling, and serum pregnancy

testing

How can we stage a patient with

lymphoma?

1971 Ann Arbor

Classification 1988 Cotswolds modification

1999 NCI criteria

2007 IWG revised guidelines

2011 workshop at 11-ICML

2013 2nd workshop at 12-ICML

2014 Lugano classification

Lugano Classification (Derived from Ann-Arbor Staging with Cotswolds- Modification)

Stage I Involvement of a single lymph node ((LN) region (eg, cervical, axillary, inguinal,

mediastinal) or lymphoid structure such as the spleen, thymus, or Waldeyer's ring.

Stage II Involvement of two or more LN regions or LN structures on the same side of the

diaphragm. Hilar nodes should be considered to be "lateralized" and when involved on

both sides, constitute stage II disease.

For the purpose of defining the number of anatomic regions, all nodal disease within

the mediastinum is considered to be a single LN region, and hilar involvement

constitutes an additional site of involvement. The number of anatomic regions should

be indicated by a subscript (eg, II-3).

Stage III Involvement of LN regions or lymphoid structures on both sides of the diaphragm. This

may be subdivided stage III-1 or III-2: stage III-1 is used for patients with involvement of

the spleen or splenic hilar, celiac, or portal nodes; and stage III-2 is used for patients

with involvement of the paraaortic, iliac, inguinal, or mesenteric nodes.

Stage IV Diffuse or disseminated involvement of one or more extranodal organs or tissue beyond

that designated E, with or without associated lymph node involvement.

Cheson BD, et al. J Clin Oncol 2014; 32: 3059-3068

Lugano Classification (Derived from Ann-Arbor Staging with Cotswolds- Modification)

Addendum A B symptoms are absent.

Addendum B B symptoms are present: fever (temperature >38ºC), drenching night sweats, and/or

unexplained loss of >10% of body weight within the preceding 6 months.

Addendum E The designation "E" refers to extranodal contiguous extension (ie, proximal or

contiguous extranodal disease) that can be encompassed within an irradiation field

appropriate for nodal disease of the same anatomic extent. More extensive extranodal

disease is designated stage IV.

Bulky disease A single nodal mass, in contrast to multiple smaller nodes, of 10 cm or ≥⅓ of the

transthoracic diameter at any level of thoracic vertebrae as determined by CT; record

the longest measurement by CT scan. The term "X" (used in the Ann Arbor staging

system) is no longer necessary.

Subscript "RS" is used to designate the stage at the time of relapse.

Patients can be clinically or pathologically staged. Splenectomy, liver biopsy, lymph

node biopsy, and/or bone marrow biopsy are mandatory for the establishment of

pathological stage. The pathologic stage at a given site is denoted by a subscript (eg, M

= bone marrow, H = liver, L = lung, O = bone, P = pleura, and D = skin).


Lymph Node Regions

Diaphragm

Supra

Infra

Ann Arbor EORTC GHSG

R Cervical/SCL

R ICL/Subpec

R axilla

L Cervical/SCL

L ICL/Subpec

L axilla

Mediastinum

R Hilum

L Hilum

Total 9 5 5

EORTC includes to combine the ICL/subpec area with axilla:

GHSG includes to combine the cervical/SCL and subpec

GHSG combined the mediastinum and bilaterally hila

Practical Staging

Criteria of Involvement

Sites Tissue site Clinical Type Test Positive finding

Lymph nodes Palpable

FDG-avid

PET-CT

Increased FDG uptake

Non-avid

CT

Unexplained node enlargement

Spleen Palpable

FDG-avid PET-CT Diffuse uptake, solitary mass,

military lesion, nodules

Non-avid CT > 13 cm in vertical length, mass,

nodules

Liver Palpable FDG-avid

PET-CT

Diffuse uptake, mass, nodules

Non-avid CT Mass, nodules


Criteria of Involvement

Sites Tissue site Clinical Type Test Positive finding

CNS Sign,

symptom

CT scan

Mass lesion(s)

MRI Leptomeningeal infiltration,

mass lesions

CSF

assessment

Cytology, flow cytometry

Other

(e.g., skin,

lung, GI tract,

bone, BM)

Site

dependent

PET/CT,

biopsy

Lymphoma involvement


Treatment of

Classical Hodgkin

Lymphoma

Prognostic Factor, Risk

Stratification, and Treatment Groups Treatment Group EORTC/LYSA GHSG

Early Stage CSI-II without risk factors

(supradiaphragmatic)

CI-II without risk factors

Intermediate stage CSI-II with ≥1 risk factors

(supradiaphragmatic)

CSI, IIa with ≥ risk factors;

CSIIB with risk factors C

and/or D, but not A/B

Advanced Stage CSIII-IV CSIIB with risk factors A and/or

B, CS III/IV

Early stage

Favorable

Unfavorable

A. Large Mediastinal mass: mediastinum-thorax ratio ≥0.35 (EORTC/LYSA), mediastinal larger than 1/3 of the

maximum thoracic width (GHSG)

B. EN disease

C. Elevated ESR: > 50 mm/h wo B symptoms, > 30 mm/h w (B symptoms; fever, night sweat, unexplained

weight loss > 10 % over 6 months

D. Nodal areas: Involvement of 4 out 5 supradiaphragmatic nodal areas (EROTC/LYSA), involvement of 3 out

of 11 nodal areas on both sides of the diaphragm (GHSG)

Eichenauer DA, et al. HemaSPhere 2018; 2: 5(e149)

Prognostic Factor, Risk Stratification, and Treatment Groups

Bröckelmann PJ, et al. Blood 2018; 131(15):1666-1678

* Elevated ESR: > 50 mm/h wo B symptoms, > 30 mm/h w (B symptoms; fever, night sweat, unexplained weight loss > 10 % over 6

months t Large Mediastinal mass: mediastinum-thorax ratio ≥0.35 (EORTC/LYSA), mediastinal larger than 1/3 of the maximum thoracic width

(GHSG)

Stage IIB with the respective RF considered advanced-stage disaese by the GHSG

Nodal areas: Involvement of 4 out 5 supradiaphragmatic nodal areas (EROTC/LYSA), involvement of 3 out of 11 nodal areas on both

sides of the diaphragm (GHSG)

Early-Stage: Favorable

2xABVD

PET-adapted Non-PET-adapted

PET-pos PET-neg

1xABVD

20 Gy-ISRT

2xBEACOPPesc

30 Gy-ISRT

EORTC/LYSA/FIL H10 study

GHSG

HD10 study

20 Gy-ISRT

ESMO Guideline

Eichenauer DA, et al. Annals of

Oncology, 2018; 29 (Suppl 4): iv19-

iv29

5 ys PFS: 87 %

10 ys OS: 94 %

5 ys PFS: 99 %

5 ys OS: 96 %

5 ys PFS: 91 %

5 ys OS: 96 %

5-point scale (Deauville Criteria)

Score 18-FDG uptake

1 No uptake

2 ≤ Mediastinal blood pool

3 > Mediastinum and ≤ liver

4 Moderately > liver at any site

5 Markedly1 > liver at any site and/or new sites of disease

X New areas of uptake unlikely to be related to lymphoma

1. i.e., maximum standardized uptake value (SUVmax) of the lesion > 2xliver uptake

Barrington SF, et al. Eur J Nucl Med Mol Imaging 2010; 37: 1824

CMR

Residual

MR

Possible

CMR

FDG uptake


2xABVD

PET-adapted

Deauville 1-3 Deauville 5

2xABVD

Refractory

disease

Biopsy

NCCN Recommendation V3.2018

20 Gy-ISRT

Deauville 4

PET/CT

20 Gy-ISRT

Neg Pos

Modified

from GHSG

HD10 study OR

or


3xABVD

PET-adapted


1xABVD

plus

30 Gy-ISRT

Refractory

disease

Biopsy


Observe

Deauville 3-4

PET/CT

Neg Pos

Modified from

RAPID,

EORTC H10

and Stanford

G4 trial

OR

1xABVD


2xABVD

PET-adapted


2xABVD (Deauville 3)

Refractory

disease

Biopsy

NCCN Recomendation V3.2018

Deauville 3-4

PET/CT Neg Pos

Modified from

RAPID,

EORTC H10

and Stanford

G4 trial

OR

1xABVD

plus

30 Gy-ISRT

2xBEACOPPe

sc (Deauville 4-5)

30 Gy-ISRT

3 ys PFS: 91 %

3 ys OS: 97 % 3 ys PFS: 95 %

3 ys OS: 99 %


Stanford Vx8weeks

PET-adapted


Refractory

disease

Biopsy


Neg Pos

Modified from

RAPID,

EORTC H10

and Stanford

G4 trial

30 Gy-IFRT

Median FU: 10.6 ys

FFP 94%

DSS 94%

OS 99%

Standard Treatment Summary in

Early Stage with Favorable

Treatment

Chemotherapy x 2 cycles + IFRT, or

Chemotherapy x 2 (3) cycles, then

– If PET neg → Observe or chemotherapy x 0-2 cycles

and/or IFRT (ISRT)

– If PET pos → IFRT (ISRT) and/or chemotherapy

(consider biopsy if high Deauville)

Chemotherapy = ABVD or BEACOPPesc.

Early-Stage: Unfavorable

2xABVD


PET-pos PET-neg

2xABVD

30 Gy-ISRT

2xBEACOPPesc

30 Gy-ISRT

EORTC/LYSA/FIL H10 study

GHSG

HD14 study

30 Gy-ISRT

ESMO Guideline

2xBEACOPPesc plus

2xABVD

or 4xABVD


Oncology, 2018; 29 (Suppl 4): iv19-

iv29

5 ys PFS: 91 %

5 ys OS: 97 %

5 ys PFS: 92 %

5 ys OS: 97 %

5 ys PFS: 92 %

5 ys OS 96 %

Early-Stage: Unfavorable

2xBEACOPPesc plus 2xABVD

PET-adapted

Biopsy

Modified

GHSG

HD14

study


ISRT

Deauville 5

Refractory

disease

Neg

Pos

Deauville 1-4


Early Stage with unfavorable

Treatment

Chemotherapy x 4 cycles + IFRT (ISRT), or

Chemotherapy x 2 cycles, then

– If PET neg → chemotherapy x 2 cycles and IFRT (ISRT)

– If PET pos → intensive chemotherapy x 2 cycles and

IFRT (ISRT)

– (or accepted as refractory disease in Deauville 5)


Advanced Stage cHL

‒ International Prognostic Score

• Age ≥45 ys

• Male gender

• Stage IV disease

• Albumin level < 4g/dL

• Hemoglobin Level < 10.5 g/dL

• Leukocytosis (WBC > 15,000/uL)

• Lymphopenia (lymphocyte count < 8 % of the

WBC and/or lymphocyte count <600/uL)

Hasenclever D, et al. NEJM 1998; 339: 1506-1514

Advanced Stage: III-IV

2xABVD


GHSG HD18

study Localized RT to

residual ≥2.5 cm

ESMO Guideline

6xBEACOPPesc

or

6xABVD

2xBEACOPPesc

RATHL

study


Oncology, 2018; 29 (Suppl 4): iv19-iv29


2xBEACOPPesc

PET-adapted

PET-pos PET-neg

2xBEACOPPesc

Observe

4xBEACOPPesc

Localized RT to residual ≥2.5 cm

ESMO Guideline

PET-scan

PET-pos PET-neg

GHSG

HD18 study


2xABVD

PET-adapted

PET-pos PET-neg

4xAVD

Observe

4xBEACOPPesc or

4xABVD

Localized RT to residual ≥2.5 cm

ESMO Guideline

PET-scan

PET-pos PET-neg

RATHL

study

Merging of different risk-adapted approaches.

Sean H. Lim, and Peter W. M. Johnson Blood 2018;131:1679-1688

RATHL/AHL2011 Lysa approaches

<60y BV-AVD x2

FDG-PET

AVD X4 BV-AVDX4

89% -

12 ms PFS: 95 vs 85%

Younes A et al. Lancet Oncol. 2013; 14(13):1348-56

https://www.ncbi.nlm.nih.gov/pubmed/24239220







ECHELON-1

study


2xBVxAVD

PET-adapted


4xBV+AVD or

Alternative treatment

Refr disease

4xBV+AVD

Observe


PET-scan

Deauville 1-2 Deuville 5 Deauville 3-4

Observe or

RT to PET+


Advanced Stage

Treatment

Chemotherapy x 6 cycles or BV plus ChT x 6 cyles, then

– If CR by CT → stop

– If PR by CT and PET neg → stop

– If PR by CT and PET pos, then

• Can receive radiotherapy → IFRT


Treatment of

Relapse/Refractory

HL

Prognostic Factors

in R/R HL as the LYSA study

High Risk

Primary refractory disease1 or relapse with two poor

prognosis factors (early relapse2 and stage III/IV

at relapse)

Intermediate Risk

Relapse with only one poor prognostic factor

(early relapse or stage III/IV at relapse)

Standart Risk

Relapse without risk factor (relapse > 12 months after

end of treatment and stage I/II disease)

Van Den Neste E, et al. Haematologica 2013; 98: 1185-1195

1Defined either by progression at any time during chemotherapy and up to 3 months after end of chemotherapy, or by failure to achieve at least PR with first-line therapy, or by persistence of significant (score 4 or 5/5) residual FDG metabolic activity using the quantitative 5-point scale Deauville score (DS). 2Defined by time to treatment failure > 3 months but < 12 months after end of first-line therapy.

OS in R/R HL according to

risk groups

(n=258)

47%

74%

51%

43%

Sibon D, et al. Haematologica 2016; 101: 474-481

Primary Refractory cHL/cHL in 1st relapse

2nd and 3rd line ChT to test chemosensivity

ASCT

Disease relapse after ASCT

Prior BV therapy or BV resistant disease

No Yes

BV CPIs or

Clinical trial

No response

Conventional salvage or

Clinical trial Consider Allo-tx

Observe

Consider Allo-tx

Sureda A&Martinez C.

EBMT Handbook 2019

HDT/ASCT Eligibility

‒ Relapsed/refractory to induction therapy • 20% to 30% of patients with Hodgkin lymphoma are relapsed/refractory to

induction regimen of ABVD

‒ Standard of care: combination chemotherapy followed by ASCT • Long-term PFS: ~ 50% of patients

‒ 70 yrs of age or younger

‒ Adequate organ function testing

‒ Able to auto collect 2 x 106 CD34+ cells

‒ Chemosensitive disease

Josting. A, et al. Ann Oncol. 2005;16:1359-65. Moskowitz

CH, et al. Blood. 2001;97:616-23; Santoro A, et al.

Haematologica 2007;92:35-41; Bartlett NL, et al. Ann Oncol.

2007;18:1071-9.

85 %

72 %

Relapsed/Refractory HL: Prognosis and Response to

Salvage Chemotherapy Before ASCT

‒ CR status at ASCT is predictive of outcome (5-yr EFS: 75% vs 31%)[1]

‒ Extranodal disease and primary refractory or relapsed disease within 1 yr are also risk factors[2]

Salvage

Regimen N ORR, % CR, %

ICE[3] 65 88 26

DHAP[4] 102 89 21

GVD[5] 91 70 19

GDP[6] 34 62 10

ICE/aug ICE[2] 97 60 (by PET)

IGEV[7] 91 81.3 53.8 (by PET)

1. Moskowitz. Blood. 2010;116:4934. 2. Moskowitz. Blood. 2012;119:1665. 3. Moskowitz. Blood. 2001;97:616. 4. Josting. Ann Oncol. 2005;16:116. 5. Bartlett. Ann Oncol. 2007;18:1071. 6. Kuruvilla. Cancer. 2006;106:353. 7. Santoro. Haematologica. 2007;92:35.

EFS by PET Status Pre-ASCT[1]

1.0

0.8

0.6

0.4

0.2

0

Yrs 0 2 4 6 8 10 12 14

Cu

mu

lati

ve E

FS

P < .0001

PET negative

PET positive

Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/

Novel Salvage Regimens for Patients

With Relapsed/Refractory HL Before

ASCT

Salvage Regimen N ORR, % CR by PET, %

BV + ICE (sequential)[1] 37 89 65

BV + augICE (sequential)[2] 45 96 76

BV + Bendamustine[3] 55 93 74

BV + ESHAP (BRESHAP)[4] 66 96 70

BV + ICE (concurrent)[5] 16 94 69

BeGEV[6] 59 83 73

1. Chen. Biol Blood Marrow Transplant. 2015;21:2136. 2. Moskowitz. Lancet Oncol. 2015;16:284. 3. LaCase. ASH 2015. Abstr 3982. 4. Garcia-Sanz. ASH 2016. Abstr 1109. 5. Cassaday. ASH 2016. Abstr 1834. 6. Santoro A. J Clin Oncol. 2016;34:3293.



Survival in Patients With HL

Relapsing After HDT/ASCT Database analysis from 5 institutions on patients with recurrent HL and

at least 1 yr of follow-up after transplantation

Arai. Leuk Lymphoma. 2013;54:2531. Slide credit: clinicaloptions.com


Agent Indications

Nivolumab

Adult patients with relapsed/refractory disease after

ASCT and brentuximab vedotin

Adult patients with relapsed/refractory disease after

≥ 3 lines of systemic therapy including ASCT Dosing: 240 mg Q2W or 480 mg Q4W

Pembrolizumab

Adult or pediatric patients with refractory disease or

who have relapsed after ≥ 3 lines of therapy

Dosing: 200 mg Q3W (adults) or 2 mg/kg Q3W (pediatric)


Current Approved Indications for PD-1

Inhibitors in Relapsed/Refractory HL


Anti-PD-1

Blokage

Phase Ib

Nivolumab Pembrolizumab

Tumoral reduction: 87 % Tumoral reduction: 65 %

17%

70%

13%

CR PR Stabil

R/R HL

Ansell S, et al NEJM 2015; Armand P, et al. 2016

16%

48%

23%

13%

CR PR Stabil Progr.

Check Point Inhibitors-Phase Ib

CheckMate-205

Total

(n=210)

n (%)

ORR 143 (68,1)

CR 63 (30,0)

PR 80 (38,1)

Stabile 40 (19,0)

Progresive 23 (11,0)

Undetermined 4 (1,9)

KEYNOTE-087

J Clin Oncol 2018; 36:1428-1439 J Clin Oncol 2017; 35:2125-2132

Total

(n=210)

N (%)

ORR 168 (69)

CR 40 (16)

PR 128 (53)

Stabile 47 (19)

Progresive 23 (9)

Undetermined 5 (2)

Check Point Inhibitors-Phase II

Mechanism Agent(s)

Antibody–drug conjugate CD25 ADC

IMiD Lenalidomide

Transcriptional pathways HDAC inhib, PIK3 inhib, mTOR inhib, BTK, Jak/STAT,

PIM kinases, galectin-1

Antibody/receptor cell therapy Anti-CD30 CAR T; CD123 (dendritic) CAR T;

bispecific Ab (CD30/CD16)

EBV-directed therapy EBV-cytotoxic T-cells, LMP-2A inhibition

Other immunotherapy (including TME) PD-L1 inhibitors; CD47-SIRP-α signaling; CSF-1 inhibitors

(macrophage)

Antiapoptotic molecules Proteasome pathway inhibition, XIAP; arsenic trioxide (restore B-cell

phenotype)

Additional approaches Adenoviral vector-transduced dendritic cells with LMP1 and LMP2

construct for latency II , CD30-targeted oncolytic viruses


A Snapshot of the Current Investigational

Therapeutic Landscape for cHL


Treatment of Elderly Patients with

cHL

NCNN guideline

Stage I/II favorable Stage I/II (unfavorable) or Stage III/IV

2xA(B)VD±2xAVD+ISRT (preferred)

VEPEMB*±ISRT

2xA(B)VD±4x AVD

6xVEPEMB*±ISRT

• Poor outcome

•B symptoms

•Poor PS

•MC type

•EBV+

•Medical comorbidities

*VEPEMB: vinblastine, cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone,

bleomycin

Treatment of NLPHL

ILROG Guideline

and NCNN

guideline

Stage IA or IIA wo RFs Other Stage

ISRT Chemotherapy plus anti-

CD20 ±ISRT

Initial Treatment

Refractory/Relapsed Disease

Biopsy

NLPHL

Localized disease

Anti-CD20

Disseminated and/or poor risk

Salvage ChT

Follow-Up After Completion

Therapy ‒ PET/CT within completion therapy

‒ Until 5 years

• History&Physical Examination: 3-6 ms for 1-2 ys, then

every 6-12 ms until year 3, then annually

• Laboratory Examination

• CBC, ESR, BFT and LFT

• TSH annually if RT to neck

• CT for neck/chest/abdomen/pelvis scan with contrast at

6, 12 and 24 mo or as indicated

• Annual influenza vaccines

Follow-Up After Completion

Therapy ‒ After 5 years

• History&Physical Examination annually

• Laboratory Examination

• Vaccines for pneumococcus, meningococcus and

H-flu if pt was treated with splenic RT or

splenectomy

• Annual influenza vaccine

• Screening for secondary neoplasia

• Cardiovascular function

• Carotis doppler (especially neck radiotherapy)

Summary in HL

‒ HL is successful story among hematological

malignancy.

‒ Today, treatment modalities and approaches are

controversial.

‒ iPET might refine the treatment (esc- or des).

‒ Incorporation of the novel agents to 1st line setting

‒ Allo-tx is still an option in highly selected patients with

relapse/refractory HL after ASCT.

eha-tsh hematology tutorial on lymphoma · epidemiology new cases 2.4.-2.5/100,000 persons (eu and...

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