Classical Hodgkin’s lymphoma

CLASSICAL HODGKIN’S LYMPHOMA:

TREATMENT STRATEGIESDR ANKIT RAIYANI

Dept. of haematologySSH, Pune.

OVERVIEW OF PRESENTATION• Staging & risk stratification• Role of PET scan• Treatment protocols (First line and second line)• ABVD protocol and its modifications• BEACOPP and its modifications• Newer agents

• Treatment of newly diagnosed HL• Early stage (Stage I/II) favourable risk• Early stage unfavourable risk• Advanced stage disease• Elderly (> 60 yr) newly diagnosed HL

• Treatment of refractory/relapseed HL

ANN ARBOR CLINICAL STAGING

RISK STRATIFICATION

Hasenclever D, et al. NEJM, 1998

ROLE OF PET SCAN• 97- 100 % HL are FDG avid• Preferable to CT for initial staging • will upstage a minority of patients and aid the interpretation of subsequent PET scan

• PET response should be reported according to Deauville criteria• 1, 2 should be considered ‘negative’ • 4, 5 considered ‘positive’• Deauville score 3 should be interpreted according to the clinical context but in many HL patients indicates

a good prognosis with standard treatment.• Interim PET scan at end of 2 cycles of chemotherapy has greatest prognostic value• Even overrules the initial IPS risk stratification• Can guide in escalation or de-escalation of further treatment

• End-of-treatment PET scan positivity: • Biopsy is advised prior to second-line therapy to confirm residual disease with score 4,5 to exclude false

positive uptake with FDG.

TREATMENT PROTOCOLS

First line protocols

• ABVD (Adriamycin, Bleomycin, Vinblastin, Dacarbazine) ± ISRT• Stanford 5 (Adriamycin, Bleomycin, Vinblastin, Vincristine, Meclorethamine, Etoposide,

Prednisone)• BEACOPP (Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine,

Procarbazine, Prednisone)•

Second line protocols ± HDT/ASCR

NEWER AGENTS• Brentuximab vedotin• Antibody-drug conjugate (ADC) directed to the protein CD30• Approved for relapsed HL• Potential uses: B-AVD, post ASCT single drug maintenance, single agent

palliation in elderly frail patients• Adverse effects: peripheral neuropathy, neutropenia• Nivolumab• Humanized IgG4 anti-PD-1 monoclonal antibody used to treat cancer.• Works as a checkpoint inhibitor, blocking a signal that would have

prevented activated T cells from attacking the cancer, thus allowing the immune system to clear the cancer

ABVD PROTOCOL

MODIFICATION OF ABVD PROTOCOL

STUDY OUTCOMEABVD AVD ABV AV

Number of

patients566 571 198 167

FFTF @ 5 years 93% 89% 81% 77%

Gr III/IV toxicity 33% 26% 28% 26%

Upfront dose reduction not recommended for treatment of cHL with ABVD

OUTCOME

ADVERSE EVENTS

BEACOPP & ESCALATED BEACOPP (NEJM 2003)

DISADVANTAGES OF BEACOPP VS ABVD• Very high rates of severe adverse events• Very high cost of treatment• No benefit in 5 yr OS as compared to ABVD• Reported PFS, OS rates may be difficult to replicate in India• Benefit in FFTF is balanced by acceptable RR of 2nd line

protocol + HDT/ASCR

TREATMENT STRATEGIES

TREATMENT OF NEWLY DIAGNOSED HL• Early stage (Stage I/II) favourable risk• Early stage unfavourable risk• Advanced stage disease

EARLY STAGE (STAGE I/II) FAVOURABLE RISK

ABVD X 2 cycles

Interim PET scan

Deauville 1-4 ISRT: 20 Gy

Deauville 5 Biopsy

Negative: ISRT 20 GyPositive: treat as

refractory disease

EARLY STAGE (I/II) UNFAVOURABLE RISK

ABVD X 4 cycles

Restage with PET scan

Deauville 1-3

ABVD X 2 cycles

AVD X 2 cycles

ISRT: 30 Gy

Deauville 4 ABVD X 2 cycles

Restage with PET scan

Deauville 5 Biopsy

Negative: ABVD X 2

cycles AND ISRT 30 - 45

GyPositive: treat as

refractory disease

ADVANCED STAGE (III/IV) DISEASE

ABVD X 2 cycles

Restage with PET

scan

Deauville 1-3

AVD X 4 cycles

Deauville 4, 5

ABVD X 4 cycles

Restage with PET

scan

Deauville 1-3

Observe or ISRT

Deauville 4ISRT to PET

positive sites

Deauville 5 Biopsy

Negative: Observe or

ISRT (30 - 45 Gy)

Positive: treat as

refractory disease

ELDERLY (> 60 YR) NEWLY DIAGNOSED HL

Non-Frail (No comorbiditie

s)

A(B)VD X 2 cycles Interim PET

Negative (1-3)

AVD X 4 cycles

Positive (4-5)Change

protocol (2nd line/

palliative)VEPEMB X 6 cycles ± ISRT

PVAG X 6 cycles ± ISRT

Frail ( Co morbiditi

es)

ChlVPPVEPEMB

Brentuximab

ISRTPalliation

TREATMENT OF REFRACTORY/RELAPSE (<1 YR) HL

Biopsy proven disease

2nd line therapy PET scan

Deauville 1-4

HDT/ASCR if eligible

Brentuximab maintenanc

e X 1 yr

ISRT/ Observe

Allogeneic SCT

Deauville 5ISRT/

Additional systemic therapy*

Allogeneic SCT

* Brentuximab, Bendamustine

CHEMOTHERAPY REGIMENS IN RELAPSED CLASSICAL HL

THANK YOU!!