DLBCL Flashcards
What are the components of the IPI score? (APpLES)
Age (>60) Performance status (2-4) LDH (>1 ULN) Extra nodal NHL (>1 site) Stage (III and IV)
What is the aa IPI?
Meant for patients 60 years and below
Stage
LDH
PS
How does the IPI correlate with OS?
IPI Low - CR 80-90%; 5y OS 70% Low intermediate - CR 60-70%; 5yOS 50% High intermediate - CR 50-60%; ;5yOS 40% High - CR 40%; 5y OS 20-30%
Describe the LNH 03-2B study
Christian Recher et al, Lancet 2011
Aim = to identify if R-ACVBP is better than RCHOP n terms of survival
Incl criteria:
- 18-59yo
- untreated DLBCL
- aaIPI =1
2 arms:
- RACVBP vs RCHOP
- both arms no RT
Results:
- 3yr EFS: 80% (RACVBP) >70%
- 3 yr PFS : 87% > 73%
- OS 90% vs 80%
- SAE 40% vs 15%
- FN rate 40% vs 10%
- Overall RR 90% vs 90%
How is R-ACVBP given?
Induction phase of 11 weeks
Consolidation phase of 19 weeks
Induction phase:
- R-ACVBP for 4 cycles Q2weekly. + IT MTX
Consolidation phase:
- Starts with 2 doses of IV MTX as Cycle 5 and 6, separated by 2 weeks
- followed by Rituximab + Ifosfamide+ Etoposide Q2weekly for 4 cycles
- ends with Cytarabine 2 doses separated by 2 weeks
What is R-ACVBP
Rituximab Doxorubicin Cyclophosphamide Vin desire Bleomycin Prednisone
What is the treatment for young patients with good prognosis DLBCL?
What is the evidence?
RCHOP x6
MInT study by Pfreundschuh Lancet Oncoogy 2006
N=800
18-60yo
0-1 risk factors (aaIPI)
Stage II-IV disease or Stage I with bulk
2 arms:
A) RCHOP x6
B) CHOP-like therapy x 6
Bulky and extra nodal sites received RT
Results:
- 3 yr f/u
- EFS 80% vs 60%
- PFS 85% vs 70%
- OS 90% vs 80%
Describe the NHL-B1 trial
Pfreundschuh Blood 2004
Aim:
CHOP-21 was standard then
Wanted to know if CHOP-14 or CHOEP-21/CHOEP-14 can improve results in those 18-60yo with good prognosis
N=700 2x2 factorial study Those in Q14days, received GCSF \+ RT to bulky disease and Extranodal writes. A) CHOP-21 B) CHOP-14 C) CHOEP-21 D) CHOEP-14
Results: CR: CHOEP >CHOP - 88% vs 80% 5y EFS: CHOEP>CHOP - 70% vs 60% OS: - interval reduction improved OS - 75% (CHOP-21); 85% (CHOP-14) - 83%( CHOEP-21); 85% (CHOEP-14)
Why RCHOP-21 and not RCHOP-14?
Cunningham Lancet 2013
CHOP-14>CHOP-21
Aim is to find out if RCHOP-14>RCHOP-21
N=1100
2 arms:
A) 6RCHOP-14 + 2R
B) 8RCHOP-21
Results: (4yr f/u)
- 2yOS 83% (RCHOP14) vs 81%
- 2yPFS ~
- ORR ~
Conclusion:
RCHOP-14 is not superior to RCHOP-21
What are the reasonable options for High Risk DLBCL in young patients?
1) RCHOP-21
2) R-EPOCH
3) R-ACVBP for young patients with 1 risk factors
- LNH03-2B by Christian Recher Lancet 2011
- OS 90% vs 80%
- 3y EFS 80% vs 70%
- 3y PFS 87% vs 73%
4) Clinical trial is an option
5) High dose-transplant in selected patients
- aa IPI high risk
- double-hit lymphomas
6) CNS prophylaxis should be considered
- IT vs HD MTX
What are the upfront transplantation trials that suggest benefits?
1) Santini et al
- Italian trial 1998
- 2 arms:
» VOCP-B–>DHAP
» VOCP-B–>HDT
2) GELA study by Haioun et al 1997
3) MILAN study by GIanni et al 1997
2arms:
- MACOP-B
- Sequential HDT
4) Milpied et al GOELAMS study 2004
2 arms:
- CHOPx8
- CEEPx2–>MTX+Cytarabine –> BEAM
Describe the Milpied transplant study
GOELAMS study NEJM 2004
Aim - to find out what is the efficacy of 1st-line intensive chemo+transplantation of Autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma
2arms:
A) HD therapy + ASCT
B) CHOP
N=200
80% completed treatment
Med f/u 4 years
Results:
- 5y EFS 55% vs 40% (CHOP)
- 5y survival rate in high-intermediate aaIPI group:
» 70% vs 40% (CHOP)
What are the trials that suggest no benefit from upfront transplantation?
1) Gisselbrecht et al 2002 2arms: - ACVBP - Shortened initial chemo+HDT Conclusion: 5y EFS and OS higher in conventional arm
2) EORTC study by Kluin et al 2001 2arms; - CHVmP/BV x6 - CHVmP/BVx3 --> HDT Conclusion: No differences in EFS/OS
3) Italian study by Martelli et al 2003 2 arms: - MACOP-B - Abbreviated MACOP-B --> HDT Conclusion: No differences in EFS and OS
4) German study by Kaiser et al 1999 2 arms: - CHEOP - CHEOP --> HDT Conclusion = no difference in EFS and OS
What is the PARMA study about?
Philip NEJM 1995
Aim: to evaluate efficacy of HD chemo–> ASCT in NHL with relapses
N=200 Relapses of NHL patients all s/p 2 cycles of conventional chemo. Those with response then randomized to: A) 4# chemo + RT B) RT+ intensive chemo + ASCT
Median f/u 5 years
RR 80% (after ASCT); 40% after chemo w/o transplant
5yEFS 46% in transplant vs 12%
OS 50% vs 30%
Conclusion:
HD Chemo+ ASCT improved EFS and OS
Describe SWOG 9704
Stiff et al NEJM 2013
Aim: to test the efficacy of ASCT during 1st remission in patients with NHL (with high-intermediate or high risk) in Rituximab era
N=400
Aa-IPI = high risk or high-intermediate risk
2 arms: A) 5CHOP - If response, assigned to: >> 3CHOP or (Control) >> 1CHOP+ASCT (transplant) B) 5RCHOP - if response, assigned to: >>3RCHOP (control) or >>1RCHOP+ASCT (Transplant)
Results:
2y PFS: 70% (Transplant group) vs 55%
2y OS: 74% vs 71%
Conclusion:
Early ASCT improved PFS in those with high-intermediate-risk or high risk disease who had a response to induction therapy
OS not improved, ?secondary to effectiveness of salvage therapy
What is the evidence to show that Rituximab improves outcomes of DLBCL in older patients?
Fisher NEJM 1993
Coiffier NEJM 2002
FIsher NEJM 1993: 4 arms comparable - CHOP - m-BACOD - ProMACE-CytaBOM - MACOP-B
Coiffier:
- RCHOP >CHOP
