dlbcl rr
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Managing relapsed and refractory
DLBCL
Andy Davies
Oxford Lymphoma Course
June 2018
DLBCL is a curable disease
Overall survival: All randomised
83.0%
82.0%
HR=0.907
p=0.549
Real World Data
Haematological Malignancies research Network 2017
Events occur early…
Overall survival from
diagnosis
Overall survival from
2 years event free
Maurer M J et al. JCO 2014;32:1066-1073
Outcomes of R-CHOP population
100%
90%
15-25% refractory
80%
5% PR patients
70%
20-30% relapses
60%
50%
40%
30%
20%
10%
0%
Coiffier and Sarkozy et al 2016
50-60% cured
How can we identify those patients that may not
respond well…?
IPI
Age greater than 60 years
Stage III or IV disease
Elevated serum LDH
ECOG > 2
More than 1 extranodal site
Age adjusted IPI
Stage
LDH
Performance status
Ziepert at al. J Clin Oncol 28:2373-2380.
Primary Refractory
Eligible for HDT
consolidation
Reinduction regimen
(I hate ‘salvage’)
Followed by HDT+PBSCT
Early relapse
Late relapse
Not eligible for HDT
• Age
• Co-morbidity
• No response to reinduction
• No stem cells at harvest
Reinduction regimen
Primary Refractory
Eligible for HDT
consolidation
Reinduction regimen
(I hate ‘salvage’)
Followed by HDT+PBSCT
Early relapse
Late relapse
Not eligible for HDT
• Age
• Co-morbidity
• No response to reinduction
• No stem cells at harvest
Reinduction regimen
PARMA Trail
(Phillip NEJM 1995)
• PARMA study (n=215
aggressive relapsed disease)
• 109 demonstrated
chemosenstivity after DHAP
x2: randomised DHAP x4
more or BEAC + ABMT
• OS 53 vs 32% at 5 years
(P=0.038)
• Time to relapse (< or > 12
months most important
prognostic factor, along
with second line aaIPI and
response to salvage PR vs
CR
Guglielmi et al, JCO 1998
PARMA TRIAL: ABMT vs DHAP
(A) Actuarial PFS curves in
responding early relapses (less
than 12 months from initial
diagnosis) according to
treatment arm (ABMT versus
DHAP).
(B) Actuarial PFS curves in
responding late relapses (more
than 12 months from initial
diagnosis) according to
treatment arm (ABMT versus
DHAP)
Evolving Standards of Care in Non-Hodgkin’s Lymphoma
clinicaloptions.com/oncology
Guideline Recommendations for
Treatment of Relapsed DLBCL
Second-line therapy in
candidates for high-dose
therapy + ASCT
– DHAP ± rituximab
– ESHAP ± rituximab
– GDP ± rituximab
– GemOx ± rituximab
– ICE ± rituximab
– MINE ± rituximab
Second-line therapy for
patients who are not
candidates for high-dose
therapy
– Clinical trial
– Rituximab
– CEPP ± rituximab
– Lenalidomide
– EPOCH ± rituximab
NCCN practice guidelines in oncology: non-Hodgkin’s lymphomas V.1.2010.
Available at: />
High Dose Chemotherapy plus ASCT:
CORAL trial experience
Gisselbrecht C et al, JCO 2010
Which Reinduction Strategy?
• DHAP, ESHAP, ICE, IVE , MIME etc ?
• Similar response rates
• CORAL study: n=396, median age 55 years.
Similar response rates R-ICE
64%
R-DHAP
63%
Factors affecting response rates:
refractory disease
relapse less than 12 months after diagnosis
International Prognostic Index (IPI) >1 than 1
Prior rituximab treatment versus no (51% v
83%)
Gisselbrecht C et al. JCO 2010;28:4184-4190
©2010 by American Society of Clinical Oncology
The limited
value of
HDT+PBCT in
relapsed DLBCL
Friedberg 2011
R-DHAP
Thieblemont C et al. JCO 2011;29:4079-4087
©2011 by American Society of Clinical Oncology
R-ICE
Differential outcome by COO
R-DHAP
R-ICE
N=232; 50% split GCB and non GCB
Thieblemont C et al. J Clin Oncol 2011;29:4079-4087
SCHOLAR-1
Crump et al. 2017
Crump et al. 2017
Crump et al. 2017
GDP…outpatient regimen
Crump et al. JCO 2014
Toxicity….
Crump et al. 2014
Better QoL
Crump et al. JCO 2014
ORCHARRD
Van Imhoff et al JCO 2016
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