Hodgkin's Lymphoma Flashcards
Tell me about the staging of Hodgkin’s Disease
I :
- Involvement of a single lymph node region (I) or
- Localized involvement of a single extra lymphatic organ/site (Ie)
II:
- Involvement of 2 or more LN regions on the same side of the diaphragm (II) or
- Localized involvement of a single associated extralymphatic organ/site and its regional LN(s), with/without involvement of other LN regions on the same side of the diaphragm (IIe)
III:
- Involvement of LN regions on both sides of the diaphragm (III) which may be accompanied by localized involvement of an associated extralymphatic organ or site (IIIe), by involvement of the spleen (IIIs) or by both (IIIe+s)
IV:
- Disseminated (Multifocal) involvement of one or more extralymphatic organs, with or without associated LN involvement, or isolated extralymphatic organ involvement with distant (Non-regional) nodal involvement
What are the B symptoms?
Unexplained fevers >38 degrees
Drenching night sweats
LOW >10% of Body weight (within 6 months prior to diagnosis)
What qualifies as a large mediastinal mass?
If tumor is 1/3 or more of the maximum thoracic diameter
What are the risk factors according to the GHSG?
Mediastinal Mass (M) Extra nodal sites (E) ESR (E) - >50 if no B symptoms - >30 if B symptoms Nodal sites must be 3 or more (N)
Tell me about the IPS score
1) Gender (Male)
2) Age 45 years and above
3) Stage IV
4) Hb 15x10^9/L
Prognostic score by Hasenclever in NEJM
- n =5000 with advanced HL
- 75% had Doxorubicin Tx and 20% had MOPP or similar
- 33% with full/selected IFRT, 2% with mantle or inverted Y-field RT, 5% with STNI
Each risk factor confers an ~7% reduction in cure rate at 5 years
Found that the higher the score, the lower the freedom from progression of disease percentage. Correlated with 5y OS as well IPS 0 = 5y FFP 84%, 5yr OS 90% IPS 1 = 5y FFP 77%, 5yr OS 90% IPS 2 = 5y FFP 70%, 5yr OS 80% IPS 3 = 5y FFP 60%, 5yr OS 80% IPS 4 = 5y FFP 50%, 5yr OS 60% IPS 5 or more = 5y FFP 40%, 5yr OS 56%
What is MOPP?
Mechlorethamine
Vincristine
Procarbazine
Prednisone
What is the Canellos trial about?
NEJM 1992
B/g: MOPP was the standard Tx for HD for ~20 years then.
Aim was to compare if newer tx regimens can be as efficacious
N= 360
Stage III/IV newly Dx HD
Pts in 1st relapse after RT was eligible
3 arms:
1) MOPP for 6-8#
2) MOPP alternating with ABVD for 12 cycles
3) ABVD for 6-8#
Results:
- ORR: 70% vs 80% vs 80%
- 5y FFS rates: 50% vs 65% vs 60%
- 5y OS: 66% vs 75% vs 73%
- OPP had more severe toxic effects on the BM and was a/w greater reductions in the prescribed doses.
Conclusion = ABVD for 6-8months was as effective as 12 months of MOPP alternating with ABVD. And both were superior to MOPP alone
What is ABVD
Doxorubicin
Bleomycin
Vinblastine
Dacarbazine
What was the evidence that led to the need to consider ABVD in the treatment of advanced HD?a
Duggan JCO 2003
N=850
Advanced HD
2 arms:
A) ABVD
2) MOPP/ABV
Results:
- CR 76% vs 80%
- 5y FFS 63% vs 66%
- 5y OS 82% vs 81%
- no diff in cardiac toxicity
- significant acute pul/hematologic rates more common with MOPP/ABV
- 9 deaths with ABVD, 15 with MOPP/ABV
- 18 secondary malignancies with ABVD, 28 with MOPP/ABV
- 13 developed MDS/Acute leukemia (11 with MOPP/ABV)
Result:
ABVD should be considered the standard regimen for Tx of advanced HD
Tell me about the Standford V regimen
Sandra Horning JCO 2002 with updated results at 5 years
N=142, Phase II
Stage III/IV or; Stage I/II with locally extensive mediastinal disease
Standford V chemo (12 weeks) –> 36 Gy RT to initial sites of bulky (5cm or more) disease or macroscopic splenic disease
Results:
- 5 yr FFP 90%, OS 96%
- no secondary leukemia
- 42 pregnancies
- among 16 who relapsed, FF2R was 70% at 5 years
Tell me about Standford V
Objectives:
- maintain/improve cure rates
- minimizing acute/long-term toxicities
Features:
- abbreviated course of treatment
- maintenance/increase in dose-intensity of individual drugs
- reduction in cumulative doses of bleomycin and doxorubicin
- marked reduction of nitrogen mustard with omission of Procarbazine
- Consolidative RT was restricted to bulky disease / macroscopic splenic disease
Regimen:
Vinblastine 6 mg/m2 + Doxorubicin 25mg/m2
- Weeks 1,3,5,7,9,11
Vincristine 1.4mg/m2 (max 2mg) + Bleomycin 5 units/m2
- Weeks 2,4,6,8,10,12
Mustard 6mg/m2
- Weeks 1,5,9
Etoposide 60mg/m2 BD on week 3, 7, 11
Prednisone 40mg/m2 daily Week 1 to 10, tapered during 11 and 12
What are the 3 risk groups in Hodgkin’s lymphoma?
Early Favorable
- Stage I/II with NO risk factors
Early Unfavorable
- Stage I/II with Risk Factors
Advanced
- Stage III/IV
- Stage IIB with large mediastinal mass or Extranodal disease
What are the risk factors in Hodgkin’s Lymphoma?
M.E.E.N
Mediastinal mass
Extranodal sites
ESR > 50 with no B symptoms; >30 with B symptoms
3 or more nodal sites
What is the IPS score for Hodgkin’s Disease?
G.A.S. H.A.L.L
Gender (male)
Age (45 or older)
Stage IV
Hb 15x10^9
What does IPS correlate with?
Hasenclever
Correlates with freedom from progression of disease & OS at 5 years
What was the evidence that made ABVD the Standard of care in the treatment of Hodgkin’s?
1) George Canellos NEJM 1992 MOPP was standard of care then. N=350 3 arms: - ABVD 6-8# - MOPP 6-8# - Alternating MOPP/ABVD for 12 weeks Results: - CR rates 70% with MOPP, 80% with ABVD and 80% with MOPP/ABVD - 5y FFS 50% vs 60% vs 60% - Life-threatening events to fatal neutropenia: 20% vs 3% vs 30%
2) David Duggan JCO 2003
- n=850
- 2 arms:
» ABVD vs MOPP/ABV
- Results:
» CR rates 70-80%~
» 5y FFS 60-70%~
» 5y OS 80%~
» More 2nd malignancies a/w MOPP/ABG
Tell me about the evidence for Standford V and RT?
Sandra Horning JCO 2002
Aim was to provide more data re: efficacy and complications using Standford V and RT
N=140
Stage III/IV/Locally extensive mediastinal stage I/II
S/p Standford V chemox12 weeks –> 36 Gy RT to initial sites of bulky (5cm or more) or macroscopic splenic disease
Results:
5y FFP 90%
OS 96%
No secondary leukemia
What is the evidence that Standford V is not better than ABVD?
1) Gordon et al Blood 2010
- 5y FFS comparable
2) Hoskin JCO 2009 UK NCRI Lymphoma study group
Aim: Comparing ABVD vs Standford V
Stage IIB/III/IV or I-IIA with bulky disease or other adverse features
N=500
Results: ORR 90%~
5yr PFS 75%~
5y OS 90%~
3) Gobbi et al Intergruppo Italiano Linfomi JCO 2005
Aim: to compare Stanford V vs MOPPEBVCAD vs ABVD to select which regimen would best support a reduced RT program
N=350 Stage IIB/III/IV
RESULTS:
- CR rates 90% (ABVD); 80%(Stanford V) and 90% (MOPPEBVCAD)
- 5y FFS 80% vs 50% vs 80%
- 5y PFS 85% vs 70% vs 90%
- 5y OS 90% vs 80% vs 90%
- myelotoxic for MOPPEBVCAD
What is HD9 about?
First published by Volker Diehl in NEJM, updated in JCO by Engert 2009
Aim: to investigate 3 combinations of chemo to find out the best regimen for advanced Hodgkin’s disease
N=1200, 15-65yo
Treatment-naive, unfavorable Stage IIB/IIIA/IIIB/IV
3 groups, each followed by RT-prn:
A) COPP-ABVD
B) BEACOPP
C) eBEACOPP
RESULTS:
5y FFTF 70% vs 80% (BEACOPP) s 90% (eBEACOPP)
5y OS 80% vs 90% vs 90%
Rates of early progression were significantly lower with eBEACOPP
10yr update: 10y FFTF 60% vs 70% s 80% 10y OS 75% vs 80% vs 90% Risk of 2nd malignancies 5% vs 8% vs 5% Overall mortality 20% vs 20% vs 10% Death due to HL 11% vs 8% vs 3%
What is HD12 about?
Peter Borchmann JCO 2011
N=1600
16-65yo
Aim: To evaluate:
1) Reduce chemo to reduce toxicities
2) Omit RT in pts responding to chemo to reduce toxicities
4arms:
1) 8# eBEACOPP +RT
2) 8# eBEACOPP - RT
3) 4# eBEACOPP + 4#baseBEACOPP + RT
4) 3# eBEACOPP +4#baseBEACOPP -RT
RT was given to:
- sites of initial bulk >5cm
- residual disease 1.5cm or more
- inadequate response to chemo
RESULTS: 5y FFTF 86% (eBEACOPP) vs 85%(4+4) 5y OS 92% vs 90% FFTF was inferior without RT. 90% vs 87% Rates of early PD 1% vs 3% (4+4)
CONCLUSION:
- 4+4 did not substantially reduce severe toxicity, but may decrease efficacy
- No evidence to omit consolidation RT for residual disease I
How did HD15 come about?
Andreas Engert
N=2200
Newly Dx advanced stage HD, 18-60yo
3 groups: A) 8#eBEACOPP B) 6#eBEACOPP C) 8#BEACOPP14 persistent mass 2.5cm or larger + PET+ --> Additional RT 30Gy
Aim is to find out:
1) 4+4 not > to 8#eBEACOPP
Hence wanted to reduce the toxicities of 8#eBEACOPP, but maintain efficacy
2) Can we use a PET-directed approach to decide who needs RT
RESULTS:
5y FFTF 84% (8#eBEACOPP) vs 90% (6#eBEAOPP) vs 85% (8#BEACOPP14)
5y PFS 86% vs 90% vs 86%
5y OS 92% vs 95% vs 94.5%
Secondary AML/MDL 3% vs 0.3% vs 1%
Death due to Tx-related toxic effects 2% vs 1% vs 2%
CONCLUSION:
6#eBEACOPP
If post-to PET-, no need RT.
How about between ABVD and BEACOPP.
Which is better?
Federico JCO 2009
Stage IIB/III/IV HL
N=300
3 arms: A) 6# ABVD B) 4#eBEACOPP + 2#baseBEACOPP C) 6# CEC (cyclo, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, Procarbazine, vinblastine, bleomycin) \+limited RT
RESULTS:
5y PFS 70% (ABVD) vs 80% (BEACOPP) vs 80% (CEC)
5y OS 80% vs 90% vs 90%
Is there any study that directly compares ABVD with BEACOPP?
Yes.
Viviani NEJM 2011
N=300
Prev untreated
Stage IIB/III/IV or IPS of 3 or more
2 arms: A) 6-8# ABVD B) 4+4 \+RT-pro Residual/PD to proceed with salvage.
RESULTS: 7y FFFP 85% (4+4) vs 70% 7y EFS 80% vs 70% 7y Rate of freedom from 2nd progression 90% vs 80% 7y OS rate 90% vs 80% (trend)
Which is better? BEAM-HSCT vs HDCT
BEAM-HSCT > HDCT in terms of FFTF, but OS did to differ significantly
Lancet 2002 study
N=160
Relapsed HD 16-60yo
2 arms:
A) 2# Dexa-BEAM –> CR/PR –> 2#Dexa-BEAM
B) 2# Dexa-BEAM –> CR/PR –> HSCT
RESULTS:
3y FFTF 55% vs 34%
No diff in OS
Is more HDCT then better?
No
JCO 2010 Andreas Josting
Aim:
ASCT had become standard of treatment then for relapsed HD.
Investigated because the intensity of treatment needed is unclear. Hence, wanted to evaluate the impact of sequential HDCT before myelo-ablative therapy.
N=240
2 groups:
A) 2#DHAP –> no PD –> BEAM+ASCT
B) 2# DHAP –> no PD –> sequential HD Cyclo/MTX/Etoposide –> BEAM+ASCT
RESULTS: 3y OS 90% vs 80% (Seq HDCT) 3y PFS 72% vs 67% 3y FFTF 71% vs 65% Significant toxicities with Seq HDCT
Is allogenic or autologous SCT better in relapsed HD?
Milpied JCO 1996
N=1200
Retrospective study
AlloBMT vs AutoBMT in relapsed HD
RESULTS: 4y OS 25% vs 40% (auto) 4y PFS 15% vs 25% (auto) 4y Relapse 60% vs 60% 4y non-relapse mortality 50% vs 30% (Auto)
Is upfront ASCT better?
No. Federico JCO 2003
Aim: determine if upfront ASCT should be done.
N=160
4#ABVD/Doxo-containing regimens –> CR or PR –> Randomized:
- HDT + ASCT
- 4# conventional chemo
RESULTS: CR 92% (HDT+ASCT) vs 89% 5y FFS 75% vs 80% 5y OS 90% vs 90% 5y RFS 88% vs 94%
CONCLUSION: no benefit with HDT and ASCT
